Next Article in Journal
Insights into Human Astrocyte Response to H5N1 Infection by Microarray Analysis
Next Article in Special Issue
Activation of DNA Damage Response Pathways during Lytic Replication of KSHV
Previous Article in Journal / Special Issue
Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Viruses
Volume 7
Issue 5
10.3390/v7052592
viruses-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry

by
Georgia Schäfer
1,2,*,
Melissa J. Blumenthal
1,2,3 and
Arieh A. Katz
1,2,3
1
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
2
Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
3
MRC/UCT Receptor Biology Research Unit, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
*
Author to whom correspondence should be addressed.
Viruses 2015, 7(5), 2592-2617; https://doi.org/10.3390/v7052592
Submission received: 23 March 2015 / Accepted: 12 May 2015 / Published: 22 May 2015
(This article belongs to the Special Issue Tumour Viruses)
Versions Notes

Abstract

:
Currently, seven viruses, namely Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1), have been described to be consistently associated with different types of human cancer. These oncogenic viruses belong to distinct viral families, display diverse cell tropism and cause different malignancies. A key to their pathogenicity is attachment to the host cell and entry in order to replicate and complete their life cycle. Interaction with the host cell during viral entry is characterized by a sequence of events, involving viral envelope and/or capsid molecules as well as cellular entry factors that are critical in target cell recognition, thereby determining cell tropism. Most oncogenic viruses initially attach to cell surface heparan sulfate proteoglycans, followed by conformational change and transfer of the viral particle to secondary high-affinity cell- and virus-specific receptors. This review summarizes the current knowledge of the host cell surface factors and molecular mechanisms underlying oncogenic virus binding and uptake by their cognate host cell(s) with the aim to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection.

1. Introduction

Cell entry is a fundamental process of the infectivity of any virus, and cell surface receptors are the critical molecules in target cell recognition determining cell tropism and species specificity [1,2]. To date, there are seven known human oncogenic viruses, namely Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1). These viruses belong to distinct viral families, display different modes of entry and host cell tropism and lead to distinct types of cancer. They all infect their specific target cells through a two-step process: the first step involves attachment to the cell surface followed by the second step of specific receptor-mediated uptake. With the exception of EBV [3] which uses the cellular receptor CD21 (or CR2) for attachment [4], all oncogenic viruses initially attach to their target cells via ubiquitously expressed cell membrane heparan sulfate proteoglycans (HSPG), also termed the “universal receptor”, which contain charged carbohydrate moieties that can interact with several viral surface glycoproteins or protein ligands expressed in the envelope and/or the capsid, respectively. This leads to accumulation of the viral particle at the cell surface and is generally followed by conformational changes ultimately facilitating viral uptake by secondary cell type- and/or virus-specific receptors. Some oncogenic viruses display simple binding and uptake involving only a small number of participating viral and/or host surface molecules, while others involve multiple viral proteins engaging with several specific receptors, co-receptors and co-factors that may vary according to cell type, implicating rather complex, highly regulated and concerted interactions [1,2].
This review summarizes the virus and host cell surface molecular interactions essential for productive viral infection and initiation of the viral life cycle of the individual oncogenic viruses that culminate in the tumorigenic process. While human immunodeficiency virus (HIV) is not considered a tumor virus per se, immunodeficiency-related malignancies play an important role in the total number of oncogenic virus-associated cancer types and will be mentioned where appropriate.

2. Epstein-Barr Virus

Epstein-Barr virus (EBV) belongs to the large and diverse family of Herpesviridae (subfamily Gammaherpesvirinae). As the first virus that has been identified as an etiologic agent for human cancer, EBV is now known to be causally associated with several B cell malignancies including Burkitt’s lymphoma, Hodgkin’s lymphoma, immunosuppression-related lymphoma, T and NK cell lymphomas as well as malignancies involving epithelial cells of the upper digestive tract, particularly nasopharyngeal and stomach carcinomas [5]. Found ubiquitously in approximately 95% of the adult population worldwide, most individuals acquire EBV infections during early childhood when EBV establishes a latent infection that persists generally asymptomatically throughout life. However, under certain circumstances when host-virus balance is not achieved such as due to immunosuppression as a result of HIV infection or in response to unrelated infections, EBV can cause malignant diseases [6]. As a predominantly orally transmitted virus, EBV has (unlike other members of the herpesvirus family) a rather narrow spectrum of potential target cells and primarily infects naïve tonsillar B cells [7] and (more rarely) oral epithelial cells [8].
Like all members of the herpesvirus family, the comparatively large EBV double-stranded linear DNA genome is packed inside a capsid which is surrounded by a tegument. This is further enclosed by a lipid envelope consisting of several conserved, as well as EBV-unique, glycoproteins. These glycoproteins play important roles during initial attachment and subsequent viral entry through interaction with specific host cell surface receptors mediating macropinocytosis [9] and lipid raft-dependent endocytosis [9,10]. It has long been known that the initial phase of EBV tethering to the host cell surface of B cells and epithelial cells occurs via the viral envelope glycoprotein gp350 (or its alternative isoform gp220) which interacts with the cellular receptor CD21 (or CR2) [4]. A recent report suggested also the involvement of CD35 as an alternative EBV attachment receptor in certain CD21-negative cells [11]. Unique among herpesviruses, gp350/220 dominates the outer viral membrane and is one of the most abundant EBV glycoproteins [12]. Although the absence of gp350/220 reduces EBV entry into epithelial and B cells, it is not absolutely required for infection [13]. In addition, the EBV transmembrane envelope glycoprotein BMRF2 has been shown to interact with β1 and α5 integrins on oral epithelial cells but not on B cells [14].
Initial tethering of EBV to either the B cell or the epithelial cell membrane eventually triggers fusion with the EBV envelope which is considered the second phase of the infection process. This requires three conserved viral glycoproteins comprising the core fusion machinery, namely the gH-gL heterodimer and gB, the latter being crucial to the fusion process as it can insert into target membranes and refold through large conformational changes to bring viral and host membranes into close proximity, resulting in the formation of a fusion pore [15]. However, activation of this core fusion machinery differs significantly for each cell type [15]. While infection of B cells occurs mainly via endocytosis followed by fusion of the virus envelope with the endocytic vesicle membrane, epithelial cells are generally entered through direct fusion with the host cell plasma membrane at the cell surface [15]. In B lymphocytes, it was found that EBV uses the host cell surface human leukocyte antigen class II (HLA class II) through binding to the viral glycoprotein gp42 which associates non-covalently with the complex of the core fusion machinery gH-gL and gB. This interaction eventually triggers fusion of the virus with the endosomal membrane, allowing entry of the tegumented capsid into the cytoplasm [16]. While the interaction between gp42, gH-gL and gB is required for EBV entry into B cells, infection of epithelial cells requires only gH-gL and gB [17]. In fact, gp42 is not only dispensable but was even found to be inhibitory for epithelial cell infection [17]. EBV fusion with the plasma membrane and entry into epithelial cells has recently been shown to involve neuropilin 1 (NRP1) which directly interacts with gB [9], as well as binding of gH-gL to αVβ6 and αVβ8 integrins [18] via recruitment and activation of receptor tyrosine kinases and signaling via the epidermal growth factor receptor (EGFR)/Akt and EGFR/extracellular-signal-regulated kinases (ERK) pathways [9]. The presence or absence of gp42 in the EBV envelope renders the virus mutually exclusive for B cell and epithelial cell entry, respectively, therefore pointing towards the role of gp42 in determining (and redirecting) EBV’s cell tropism [17].

3. Kaposi’s Sarcoma-Associated Herpes Virus

Kaposi’s sarcoma-associated herpes virus (KSHV) or human herpesvirus-8 (HHV-8) is a gamma-2 or rhadinovirus subfamily herpesvirus (Herpesviridae family) that causes two types of malignancies: the vascular tumor known as Kaposi’s Sarcoma (KS), including classical KS, African-endemic KS, iatrogenic KS and epidemic or AIDS-associated KS, as well as B cell malignancies including multicentric Castleman disease and primary effusion lymphoma [19,20,21]. With the onset of the AIDS epidemic, immunodeficiency-related neoplasias have been steadily on the rise, and KS is now considered the most common AIDS-related malignancy worldwide [22,23,24]. Unlike EBV, KSHV is not a ubiquitous virus but is most prevalent in African populations [25].
KSHV DNA sequences can be detected in various body fluids such as blood, plasma, semen, and saliva. However, transmission of the infection seems to mainly occur through contaminated saliva [26,27,28,29,30,31]. KSHV infects a variety of target cells, such as activated B cells, endothelial cells, monocytes (including macrophages and dendritic cells), fibroblasts and epithelial cells [32].
As a member of the herpesvirus family, KSHV structure shows close similarities to EBV as described above, with the KSHV double-stranded linear DNA genome packed inside a capsid which is surrounded by a tegument and further enclosed by a lipid envelope, the latter consisting of five conserved glycoproteins, namely gB, gH, gL, gM and gN, as well as several KSHV-unique lytic cycle associated glycoproteins such as ORF4 and gpK8.1A [32,33]. Although KSHV displays broad cell tropism with the available host cell surface molecules determining the particular cell-type specific mode of entry via engagement with multiple KSHV glycoproteins [34], generally, glycoproteins gB and gpK8.1A function as key molecules in the initial attachment of the virus to the cell surface [35], while the non-covalently linked gH-gL complex is indispensable for subsequent KSHV entry [36].
In the initial phase of the infectious cell entry, KSHV attaches to host cell surface HSPGs mostly via gB and gpK8.1A [35,37], possibly followed by conformational changes in viral glycoproteins allowing access to specific entry receptors which function in the second phase of the infection [38]. According to cell tropism and entry pathway, these entry receptors vary and/or are utilized by KSHV in different combinations. Several studies on human fibroblasts and human endothelial cells demonstrated the necessity of viral gB engagement with the integrins α3β1, αVβ3, αVβ5 for cell entry [39,40], and recently also the interaction of gB with integrin α9β1 has been discussed [41]. Multiple integrin receptors can interact with the glutamate/cystine exchange transporter xCT, which has been identified as a fusion-entry receptor mediating KSHV-induced endocytic events [39,42]. However, it is yet unknown which KSHV glycoprotein interacts with xCT. During infection of dendritic cells, macrophages and activated B cells, KSHV has been reported to utilize the C-type lectin DC-SIGN [43,44] via the highly mannosylated glycoprotein gB [45]. Crucial for the entry process of KSHV into endothelial cells and downstream signaling is the recently identified ephrin receptor tyrosine kinase A2 (EPHA2) at the host cell membrane [36,46] that binds the gH-gL dimer. Binding to EPHA2 follows KSHVs initial interaction with integrins, leading to EPHA2 phosphorylation, coordinated integrin-associated downstream signaling and endocytosis, which enables KSHV entry and subsequent infection [47].
Depending on the targeted cell type, KSHV has been reported to induce different routes of endocytic uptake, particularly macropinocytosis and clathrin-mediated endocytosis [32]. In endothelial cells, actin-dependent, dynamin-independent macropinocytosis has been described as a major route for productive KSHV infection [48]. This is in contrast to the route of entry in human fibroblasts, which occurs via dynamin-dependent, clathrin-mediated endocytosis [48,49]. Downstream of the described surface-mediated events, KSHV infection has been found to be dependent on activation of Focal adhesion kinase (FAK) [50], phosphorylated Src [51] and phosphoinositide 3-kinase (PI3K) signaling [52].

4. Human Papillomavirus

Papillomaviruses belong to the diverse family of Papillomaviridae comprising predominantly squamous-epitheliotropic, non-enveloped, small DNA viruses, which are ubiquitous throughout the world. There are more than 100 different types of human papillomaviruses (HPVs), which can be broadly divided into the types infecting mucosal epithelium and those infecting cutaneous epithelium [53]. HPV infections particularly affect squamous cells of the anogenital region, the skin and the upper aerodigestive tract. Depending on their ability to cause malignant cell transformation, HPVs have been grouped into low-risk and high-risk genotypes with HPV 16 and 18 being the most common oncogenic types world-wide. Indeed, HPVs are the most prevalent causes of sexually transmitted infections in the world and are known to be associated with the development of multiple carcinomas with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs [54].
HPV is generally not passed through body fluids but is rather transmitted by direct skin-to-skin contact. Viral infection predominantly occurs in the mitotically active basal layer of keratinocytes attached to the basement membrane of the host’s cutaneous and mucosal epithelia. While entry and infection in the upper epithelial layers has not been conclusively ruled out, cell cycle progression through early stages of mitosis was found to be critical for successful HPV infection providing a reason why HPV seems to infect only undifferentiated proliferating cells [55]. As the life cycle of HPV is dependent on the differentiation of basal cells into keratinocytes, the virus is highly tissue-restricted and thought to reach its cellular targets through disruptions of the integrity of the stratified or columnar epithelium that exposes the basal layer of cells for infection [56].
The icosahedral capsid coat of HPV containing the circular double-stranded DNA viral genome is composed of two structural proteins, the major capsid protein L1, and the minor capsid protein L2 which is mostly hidden from the capsid surface [57]. Although both L1 and L2, to different extents, are involved in the attachment of the virus to basal keratinocytes, the exact mechanism and receptors used by HPV to specifically bind to and infect epithelial cells is still highly debated. Differing experimental approaches and types of HPV particles used challenge the consistencies of the observations between studies [58]. The current two-step entry model entails that HPV, like many pathogens, initially binds to HSPGs at the epithelial cell surface or on the basement membrane which serve as primary attachment receptors [56,59,60,61,62]. Indeed, cells lacking HSPGs display greatly reduced HPV uptake [63,64,65]. In addition, laminin-5 secreted onto the extracellular matrix by keratinocytes has been proposed as a high-affinity initial attachment molecule [66]. The initial L1-mediated attachment is thought to induce conformational changes in the virus capsid through sequential engagement of multiple heparan sulfate (HS) binding sites eventually resulting in loss of affinity to the primary attachment receptor and transfer of the virus to an as yet unidentified secondary receptor [67]. The conformational changes in the virus capsid are thought to be brought about by cyclophilin B [68], thereby increasing the exposure of the otherwise hidden amino terminal portion of the L2 protein which contains a highly conserved consensus site for the proprotein convertase furin. Cleavage of L2 by furin is thought to be necessary for infection although it is debated whether it is a prerequisite at the early stage of binding and entry, or for endosome escape at later stages during the infection process [69,70]. Several secondary, predominantly L1-specific, receptors have been proposed, such as α6 integrin [71,72], EGFR and keratinocyte growth factor receptor (KGFR) [73] and tetraspanins [74]. Interestingly, the tetraspanin CD151 was found to be highly expressed in the basal layers of human cervical mucosa which—in association with integrins—may further explain the tissue-tropism of HPV16 infection [75]. Moreover, the annexin A2 heterotetramer (AIIt), a multifunctional protein involved in diverse cellular processes [76], has been implicated to act as an L2-specific receptor [77], regulating entry and intracellular trafficking of the virus [78].
Once bound to its specific uptake receptors, HPV enters the cell through a comparatively very slow asynchronous actin-dependent, and clathrin-, caveolin-, cholesterol-, and dynamin-independent endocytic process, with an average half-time of 12 h [79]. Internalization was found to be dependent on several signaling molecules such as EGFR, protein kinase C (PKC), p21-activated kinase 1 (PAK-1), the PI3K/Akt/mTOR pathway, and other yet unidentified tyrosine and serine/threonine kinases [79,80].
While there is no clear evidence for additive and/or alternative pathways, it is tempting to speculate that multiple internalization routes exist given the multitude of potential molecules involved in HPV binding and uptake. This is particularly interesting in the context of other viral entry pathways using similar entry molecules to HPV, for example cytomegalovirus (CMV) which infects cells via HSPGs (initial attachment), EGFR, integrins and/or annexin A2 (specific uptake) [81]; or Hepatitis C Virus (HCV) which employs HSPGs, EGFR, tetraspanins and similar intracellular signaling molecules ([82,83,84,85,86] and below). Moreover, the ability of different HPV types to species-specifically interact with individual binding and/or uptake molecules adds to the complexity of HPV entry and may provide an explanation of anatomical-site preferences of a given HPV type [87].

5. Merkel Cell Polyomavirus

Merkel cell polyomavirus (MCPyV) is the most recently identified member of the Polyomaviridae family which consists of non-enveloped, icosahedral, double-stranded DNA viruses capable of infecting a variety of species [88] including humans and having tumorigenic potential [88,89]. Merkel cell carcinoma (MCC) is generally found in sun-exposed areas of the skin, most commonly the head and neck [90]. MCPyV was first isolated from MCC tumors in 2008 [91] using Digital Transcriptome Subtraction [92]. Since then, a compelling line of evidence has been established for MCPyV as the causative agent of MCC, and 64%–88% of primary MCC tumors as well as metastases harbor MCPyV DNA and express MCPyV gene products [91,93,94,95,96,97,98,99,100]. MCC is a relatively rare, albeit severe, human cancer, predominantly presenting in elderly, Caucasian people [101] with suppressed immune systems and also HIV-infected individuals [102]. The incidence of MCC has drastically increased in the last two decades, presumably due to the increasing incidence of HIV/AIDS [90,101].
MCPyV is common in the population [99,103,104,105] and has a worldwide distribution [97,99,103,104,105,106,107]. MCPyV has been detected in children and seroprevalence found to gradually increase with age [105,106]. A correlation between siblings as well as mothers and small children was noted, suggesting transmission via close contact of skin and saliva during early childhood [106]. The virus has been detected in a diverse range of human tissues, although at significantly lower levels than in MCC tumors [108]. Keratinocytes are suspected to be the primary cells infected by MCPyV, supported by the chronic shedding of MCPyV from the skin [103]. However, the relationship between the cells that MCPyV infects and those that it transforms to give rise to MCC is currently unclear. MCC was thought to originate from Merkel cells due to similar expression patterns; however, this has come under debate due to differences in histomorphologic growth patterns and the discovery of markers previously thought to be of neuroendocrine cells, in a subset of lymophomas. A recent study proposes pro/pre- or pre-B cells as the cells of MCC due to the expression of terminal deoxynucleotidyl transferase (TdT) and paired box gene 5 (PAX5) in 72.8% and 100% of MCCs tested, respectively [109]. Jankowski et al. add that dysregulated expression of transcription factors in an epithelial cell could equally explain this expression pattern [110].
The MCPyV capsid consists of the structural proteins VP1 and VP2 in a ratio of 5:2 for native virions, while the VP3 minor capsid protein found in other polyomaviruses is undetectable in MCPyV [91,111]. Essential for MCPyV entry are pentameric knobs made up of the major capsid protein VP1 which bind to cellular receptors [112]. VP2 is essential for infectious entry in some cell types in vitro but others were transduced with MCPyV pseudovirions deficient in VP2. Knockdown of VP2 did not affect virion assembly, packaging of DNA or attachment to a target cell, indicating that the role of VP2 is in post-attachment entry. Myristoylation of VP2 has been shown to be important for infection of some cell types [111]. Current evidence points to a 2-step attachment-and-entry process for MCPyV whereby VP1 initially attaches to sulfated glycosaminoglycans, in particular heparan sulfate [113]. This is followed by transferal to a sialylated glycan which serves as a secondary post-attachment co-receptor and may mediate uptake by the cell. In concordance with the attachment mechanisms of other polyomaviruses [114,115,116,117], the ganglioside Gt1b was the first proposed receptor for MCPyV which was shown to interact with the sialic acid moieties on the Gt1b carbohydrate chain [118]. However, this was later disproved as Lec2 cells that lack sialylated glycans were found to bind MCPyV pseudovirions but were not productively infected [113]. The recently solved crystal structure of MCPyV major capsid protein VP1 showed a sialic acid binding site that, through mutation studies, was identified as having a role in post-attachment infection, not initial attachment. This sialic acid binding site differs from those of the previously characterized polyomaviruses BKPyV and murine polyomavirus for which sialylated glycans are primary attachment receptors and which is distinct from the yet unidentified binding site for sulfated glycosaminoglycans [112].
MCPyV seems to enter its target cells very slowly and asynchronously [119]. Eventually, viral replication takes place in the host cell nucleus, establishing productive infection. However, the events following penetration of the cell membrane and delivery of the encapsidated DNA to the nucleus are not yet fully established due to the lack of a reliable system to study MCPyV infection in cultured cells, especially with regard to infectivity and cell type tropism [119].

6. Hepatitis B Virus

Hepatitis B Virus (HBV) is the prototype of the Hepadnaviridae family of small, enveloped viruses that are tropic for the liver [120]. The virus is ubiquitous with a global distribution. HBV infection usually persists throughout the lifetime of the host as a result of noncytocidal infection of hepatocytes and their shedding of infectious virus into the blood stream and body fluids which represents the main route of transmission. Host immune response to the infection results in liver damage and scarring, creating a favorable environment for oncogenesis with a lifetime risk of developing liver cancer of 10%–25% in patients with chronic HBV infections [121]. HBV accounts for approximately 50% of hepatocellular carcinoma world-wide, which occurs mainly in less developed regions [122].
HBV is the smallest known enveloped virus. It is comprised of an icosahedral nucleocapsid containing the partially double-stranded, relaxed circular DNA (rcDNA) surrounded by a compact envelope [123,124]. The envelope consists of a host-derived cholesterol-rich lipid bilayer in which three surface glycoproteins, encoded by the same open reading frame, are embedded: L (large), M (middle) and S (small) [123,125,126]. The N-terminal preS1 domain of the L-protein is myristoylated at glycine 2 and this post-translational modification has been shown to be essential for viral infectivity [127,128,129]. Mutants lacking myristoylation are capable of normal viral assembly but are non-infectious to human hepatocytes [127,129].
Investigations into the entry mechanisms of HBV were hampered by the lack of a workable HBV infection system. Established human hepatoma cell lines were found to be unsusceptible to HBV and primary human hepatocyte cultures (PHHs) obtained from surgically resected liver pieces were susceptible but limited in availability, difficult to work with and variable in their preparation [130]. Primary hepatocyte cultures from the northern treeshrew Tupaia belangeri (PTH), which were shown to be susceptible to HBV, and a newly derived HepaRG hepatoma-derived cell line, provided the required infection systems to progress understanding of the mechanisms of HBV entry [131,132,133].
In 2005, Heparin Chromatography was reported as a method for purifying HBV virions from blood plasma, noting that heparin was a close homologue of liver heparan sulfate [134]. HSPGs were subsequently shown to act as an initial attachment receptor for HBV. The addition of heparin or dextran sulfate inhibits HBV infection, presumably by outcompeting HSPG for HBV binding, whereas a low-sulfated form of chondroitin sulfate does not [135]. Interestingly, liver-HS is also the binding receptor for other liver-targeting pathogens such as HCV (see below), dengue virus and malaria circumsporozoite [136,137,138].
Following attachment to HSPGs in the initial phase, HBV uptake through a specific entry receptor in the second phase of infection has long been elusive. While other viruses use a multitude of receptors for entry, only one candidate, namely sodium taurocholate co-transporting polypeptide (NTCP) [139,140,141], has been identified as a functional uptake receptor for HBV [139,140,141], initially using a synthetic preS1 construct together with PTH hepatocytes as target cells [139]. Importantly, susceptibility to HBV can be conferred on non-susceptible liver cell lines by transfecting them with NTCP [139,140,141]. NTCP is found exclusively in hepatocytes which explains the highly specific HBV tropism for the liver.
HBV uptake into hepatocytes is thought to be regulated by clathrin-mediated endocytosis of the NTCP-HBV complex. PreS1 of the HBV L-protein interacts with clathrin heavy chain and clathrin adaptor protein AP-2. Employing sh-RNA knockdown of these molecules attenuated infection of a human primary hepatocyte cell line. In addition, treatment with an inhibitor of clathrin mediated endocytosis, chlorpromazine, inhibited HBV infection [142] presumably due to inhibition of NTCP endocytosis [143].

7. Hepatitis C Virus

Hepatitis C Virus (HCV) is a member of the Flaviviridae family—enveloped RNA viruses which are characterized by single-stranded RNA of positive polarity embedded in a capsid which is wrapped in a lipid and protein envelope. Like HBV, HCV is a hepatotropic virus and a major cause of chronic hepatitis, progressive liver disease and hepatocellular carcinoma worldwide. While about 3% of the global population is affected by HCV, approximately 1%–4% develop liver cancer, predominantly in Europe and Asia [122,144,145]. HCV is primarily transmitted through blood and infected blood products with very low risk of sexual or vertical transmission [146]. The virus can initiate infection of the host cell as cell-free particle and/or via cell-cell contact [147].
The viral envelope consists of host phosphatidylcholine, cholesterol-rich and triglyceride-rich lipoproteins incorporating host Very-Low Density Lipoprotein (VLDL) components such as apolipoproteins (Apos) AI, B, and E, as well as the viral glycoproteins E1 and E2 that form a heterodimer. These moeities are essential for infectivity of mature circulating HCV particles [148,149]. Unlike HBV entry as described above, infection of hepatocytes by HCV is more complex and involves multiple host cell molecules, suggesting a highly orchestrated process. However, initial attachment and concentrating of the virus to the hepatocyte surface is similar for both HBV and HCV and occurs via HSPGs which is mediated by the HCV glycoprotein E2 and host ApoE present in the viral envelope [136,150]. Subsequent internalization has been found to be mediated by a complex interplay between the HCV glycoproteins E1/E2 and several cellular factors which are important in defining HCV tissue specificity [151] including tetraspanin CD81, Scavenger Receptor B1 (SR-B1), and the tight junction proteins claudin-1 and occludin (reviewed in [152,153]). However, the sequential order of HCV-receptor interactions during the uptake phase is not well understood. It is hypothesized that the lipid-rich nature of the HCV particle may favor an initial interaction with SR-B1 possibly leading to conformational changes in the HCV glycoproteins [153], thereby contributing to HCV entry in an High Density Lipoprotein (HDL)-dependent manner [154,155]. SR-B1 is a lipoprotein receptor which is expressed primarily in liver and nonplacental steroidogenic tissues, and mediates both the selective uptake of cholesteryl esters and the efflux of cholesterol [156]. Moreover, several reports have indicated a role of SR-B1 in microbial recognition and uptake, such as that of M. tuberculosis [157] and P. falciparum [158]. While SR-B1 might function independently during intermediate steps of HCV infection by preparing the virus for hepatocyte entry, host surface molecules tetraspanin CD81 and claudin-1 form complexes that facilitate HCV uptake later in the entry process [159]. It is thought that HCV directly interacts with CD81 (and only indirectly with claudin-1 [160]) leading to further conformational rearrangement of the HCV E1/E2 glycoproteins [161]. Required for productive HCV infection is also the recently identified tight junction protein occludin [162,163,164], suggesting that HCV entry predominantly occurs at hepatocyte tight junctions [153]. Interestingly, Niemann-Pick C1-like cholesterol receptor (NPC1L1) [165] and the iron uptake receptor transferrin receptor 1 [166] have been assigned to play accessory but essential roles in HCV uptake. Lastly, the receptor tyrosine kinases EGFR and EPHA2 have recently been found to be involved in mediating HCV entry by regulating CD81-claudin-1 co-receptor associations [85,86], illustrating once more the complex involvement of multiple host surface molecules in HCV uptake.
Following the interactions with the host receptors, HCV enters the cell via clathrin- and dynamin-dependent endocytic pathways [82,84] with downstream activation of Rho GTPase family members Rac, Rho and cell division cycle 42 (CDC42) and mitogen-activated protein kinase (MAPK) signaling cascades [83].

8. Human T Cell Lymphotropic Virus Type 1

Human T cell lymphotropic Virus Type-1 (HTLV-1) is a member of the Retroviridae family of single stranded RNA viruses that replicate in the host via reverse transcription [167,168,169]. As the etiological agent of Adult T cell lymphoma, HTLV-1 was independently described in the early 1980s [167,168,169,170] and became the first oncogenic retrovirus to be discovered. Chronic myelopathy and specific types of uveitis (HTLV-uveitis) have also since been associated with HTLV-1 infection [167,168,169,170,171,172].
HTLV-1 is endemic to south-western Japan [173] with a prevalence, in some areas, of >10% of the population [174] and is also prevalent in sub-Saharan Africa, the Caribbean, Iran and South America (reviewed in [175]). However, most HTLV-1 prevalence studies are based on screening of blood donors, pregnant women or sub-populations within endemic areas which introduces screening bias and limits an accurate estimation of number of infections which is thought to be greater than 20 million people [176].
HTLV-1 is transmitted by the introduction of cell-associated virus from mother to child through breast feeding [177], through sexual intercourse [178,179] or via blood or blood products [180]. The primary target cells of HTLV-1 are CD4+ T cells, however other cell types, such as dendritic cells [181], CD8+ T cells [182] and endothelial cells [183] can be infected. Cell-free virus is thought to be poorly infectious and is found at minimal levels in the peripheral blood even in individuals with a high percentage of T cells containing integrated virus [184]. Dendritic cells have, however, been shown to be susceptible to infection by cell-free virus and capable of rapidly transmitting it to T cells [181,185]. Cell-to-cell transmission accounts for the early spread of HTLV-1 in an individual. At a later stage, HTLV-1 infection persists through mitotic division of infected cells [186].
The HTLV-1 virion, like other retroviruses, is surrounded by a proteo-lipid envelope containing proteins with transmembrane (TM) and surface (SU) subunits. Most important for HTLV-1 infection is the product of the viral env gene which is cleaved by cellular proteases into the non-covalently linked TM subunit gp21 and the extracellular SU subunit gp46 [187], the latter consisting of an N-terminal Receptor-Binding Domain (RBD), a mid Proline rich region (PRR) and a C-terminal domain [187].
The current understanding of HTLV-1 entry into host cells is a multi-receptor model involving cellular HSPGs, NRP1 and glucose transporter-1 (GLUT-1) receptors through viral attachment and virus/cell fusion [188]. Initial attachment is mediated by interaction between the C-terminal domain of viral gp46 and HS moieties of cell surface HSPGs [189,190] of activated CD4+ T cells [191] or dendritic cells [181]. The length of HS chains has been found to affect the susceptibility of cells to HTLV-1 entry. Shorter HS chains facilitate closer attachment of the HTLV-1 virion to the target cell [192]. This eventually leads to viral binding to NRP1, a cell surface co-receptor for multiple growth factors such as vascular endothelial growth factor (VEGF), which can itself bind heparan sulfate [193,194,195]. The viral gp46 RBD contains the KPxR motif that has been identified as the NRP1 binding site [185]. The NRP1 b-domain which binds VEGF is required for HTLV-1 entry, and gp46 SU binding to NRP1 is inhibited by the HSPG binding domain of VEGF, indicating that HTLV-1 utilizes HSPG and NRP1 in complex by molecular mimicry of VEGF, particularly in cell types that normally lack VEGF production [185].
Subsequent to stable binding of HTLV-1 to HSPGs and NRP1, GLUT-1 binding sites on gp46 are exposed, presumably as a result of conformational changes in gp46 [188]. HTLV-1 binds GLUT-1 at its large extracellular loop (ECL1) [196,197]. The amino acid residues in the RBD of gp46 that are essential for GLUT-1 binding have been shown to be distinct from the binding sites of NRP1 and HSPGs, indicative of the formation of a multi-receptor complex [193,197]. Antibodies to GLUT-1 attenuate HTLV-1 fusion and infection but not binding to CD4+ T cells, indicating that binding to GLUT-1 is essential for fusion [196].
Cell-to-cell transmission requires cell contact between an infected cell and an uninfected cell and the formation of a Virological Synapse (VS) [198]. Igakura et al. observed that infected T cells formed conjugates with neighboring uninfected cells which induced polarization of the microtubule organization center (MTOC) to the point of contact [198]. Polarization of the MTOC is promoted by the interaction of intercellular adhesion molecule-1 or -3 (ICAM-1, ICAM-3) or vascular cell adhesion molecule-1 (VCAM-1) on infected cells with β-integrins, such as lymphocyte function-associated antigen-1 (LFA-1) on uninfected cells [199,200,201]. The HTLV-1 Env and Gag proteins and the HTLV-1 genome accumulate at the point of contact and then egress into the VS and interact with receptors on the conjugated, uninfected cell. NRP1 and GLUT-1 have been shown to co-localize at the point of contact and presumably promote the formation of the VS [193,202] which is also facilitated by the HTLV-1 encoded transcriptional transactivator protein Tax (Transcriptional Activator of pX region) [203]. Little is known about the mechanism at play to facilitate uptake of HTLV-1 subsequent to transmission across the VS, although it is speculated that this occurs via endocytosis of the virus as is the case for HIV [186].

9. Conclusion

With the discovery of oncogenic viruses as the etiologic agents of various human cancers, targeting viral entry is particularly relevant in prevention of viral infection, antiviral therapy, vaccine development, and ultimately cancer prevention. The knowledge of the viral particle components and the host cell entry factors and their specific interactions can enable the design of efficient antiviral strategies. These strategies can include vaccines against distinct viral proteins required for viral entry or small molecules that target the host entry factors or the interactions between both. While almost all oncogenic viruses use HSPGs during initial attachment to their target cells, the specific uptake receptors differ considerably between the individual viruses (Table 1). This review summarized the current knowledge of the host factors required for oncogenic virus uptake in order to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection.
Table
Table 1. Summary of cellular and molecular factors involved in human oncogenic virus uptake.
Table 1. Summary of cellular and molecular factors involved in human oncogenic virus uptake.
VirusInfected cell typeAssociated type of cancerAttachment receptor(s)Proposed uptake receptor(s) and/or co-receptorsUptake mechanism
EBVB cells, oropharyngeal epithelial cellsBurkitt’s, Hodgkin’s, immunosuppression-related, T and NK cell lymphomas, nasopharyngeal and stomach carcinomasCD21 (CR2), CD35, β1 and α5 integrinsHLA class II molecules, αVβ6, αVβ8 integrins, NRP1macropinocytosis and lipid raft-dependent endocytosis (epithelial cells)
KSHVendothelial cells, B cells, monocytes (macrophages and dendritic cells), fibroblasts, epithelial cellsKS, B cell malignanciesHSPGsα3β1, αVβ3, αVβ5, α9β1 integrins, xCT, DC-SIGN EPHA2actin-dependent, dynamin-independent macro-pinocytosis (endothelial cells), dynamin-dependent, clathrin-mediated endocytosis (fibroblasts),
HPVepithelial cells (particularly basal keratinocytes)cervical, anal, head and neck cancerHSPGs, laminin-5α6 integrin, EGFR, KGFR, tetraspanins, AIItactin-dependent, clathrin- and lipid raft-independent endocytosis
MCPyVkeratinocytesMerkel cell carcinomasulfated glycosamino-glycans (most likely HSPGs)sialylated glycansunknown
HBVhepatocyteshepatocellular carcinomaHSPGsNTCPclathrin-mediated endocytosis
HCVhepatocyteshepatocellular carcinomaHSPGstetraspanin CD81, SR-B1, claudin-1, occludin, NPC1L1, transferrin receptor 1, EGFR, EPHA2clathrin- and dynamin-dependent endocytosis
HTLV-1CD4+ T cells (dendritic cells, CD8+ T cells, endothelial cells)Adult T-cell leukemiaHSPGs/NRP1GLUT-1viral synapse formation possibly followed by endocytosis
Listed are all known cellular factors involved in binding and uptake of the seven human tumor viruses described to date. Note that multiple molecules can be engaged by a particular virus in different combinations and not necessarily all at the same time. Please refer to the text for references.

Acknowledgments

G.S. was funded by grants from the Poliomyelitis Research Foundation (PRF), the Cancer Association of South Africa (CANSA), the South African Medical Research Council (SA-MRC) and the National Research Foundation (NRF) of South Africa; M.J.B. received an MSc bursary from the NRF; A.A.K. was funded by the SA-MRC, CANSA and PRF.

Author Contributions

G.S., M.J.B. and A.A.K. wrote the paper.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Marsh, M.; Helenius, A. Virus entry: Open sesame. Cell 2006, 124, 729–740. [Google Scholar] [CrossRef] [PubMed]
  2. Sieczkarski, S.B.; Whittaker, G.R. Viral entry. Curr. Top. Microbiol. Immunol. 2005, 285, 1–23. [Google Scholar] [PubMed]
  3. Shukla, D.; Spear, P.G. Herpesviruses and heparan sulfate: An intimate relationship in aid of viral entry. J. Clin. Investig. 2001, 108, 503–510. [Google Scholar] [CrossRef] [PubMed]
  4. Tanner, J.; Weis, J.; Fearon, D.; Whang, Y.; Kieff, E. Epstein-Barr virus gp350/220 binding to the B lymphocyte C3D receptor mediates adsorption, capping, and endocytosis. Cell 1987, 50, 203–213. [Google Scholar] [CrossRef] [PubMed]
  5. Thompson, M.P.; Kurzrock, R. Epstein-Barr virus and cancer. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2004, 10, 803–821. [Google Scholar] [CrossRef]
  6. Odumade, O.A.; Hogquist, K.A.; Balfour, H.H., Jr. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin. Microbiol. Rev. 2011, 24, 193–209. [Google Scholar] [CrossRef] [PubMed]
  7. Klein, G.; Klein, E.; Kashuba, E. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes. Biochem. Biophys. Res. Commun. 2010, 396, 67–73. [Google Scholar] [CrossRef] [PubMed]
  8. Hutt-Fletcher, L.M. Epstein-Barr virus entry. J. Virol. 2007, 81, 7825–7832. [Google Scholar] [CrossRef] [PubMed]
  9. Wang, H.B.; Zhang, H.; Zhang, J.P.; Li, Y.; Zhao, B.; Feng, G.K.; Du, Y.; Xiong, D.; Zhong, Q.; Liu, W.L.; et al. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells. Nat. Commun. 2015, 6, 6240. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  10. Katzman, R.B.; Longnecker, R. Cholesterol-dependent infection of Burkitt’s lymphoma cell lines by Epstein-Barr virus. J. Gen. Virol. 2003, 84, 2987–2992. [Google Scholar] [CrossRef] [PubMed]
  11. Ogembo, J.G.; Kannan, L.; Ghiran, I.; Nicholson-Weller, A.; Finberg, R.W.; Tsokos, G.C.; Fingeroth, J.D. Human complement receptor type 1/CD35 is an Epstein-Barr virus receptor. Cell Rep. 2013, 3, 371–385. [Google Scholar] [CrossRef] [PubMed]
  12. Edson, C.M.; Thorley-Lawson, D.A. Epstein-Barr virus membrane antigens: Characterization, distribution, and strain differences. J. Virol. 1981, 39, 172–184. [Google Scholar] [PubMed]
  13. Janz, A.; Oezel, M.; Kurzeder, C.; Mautner, J.; Pich, D.; Kost, M.; Hammerschmidt, W.; Delecluse, H.J. Infectious Epstein-Barr virus lacking major glycoprotein BLLF1 (gp350/220) demonstrates the existence of additional viral ligands. J. Virol. 2000, 74, 10142–10152. [Google Scholar] [CrossRef] [PubMed]
  14. Xiao, J.; Palefsky, J.M.; Herrera, R.; Berline, J.; Tugizov, S.M. The Epstein-Barr virus BMRF-2 protein facilitates virus attachment to oral epithelial cells. Virology 2008, 370, 430–442. [Google Scholar] [CrossRef] [PubMed]
  15. Connolly, S.A.; Jackson, J.O.; Jardetzky, T.S.; Longnecker, R. Fusing structure and function: A structural view of the herpesvirus entry machinery. Nat. Rev. Microbiol. 2011, 9, 369–381. [Google Scholar] [CrossRef] [PubMed]
  16. Li, Q.; Spriggs, M.K.; Kovats, S.; Turk, S.M.; Comeau, M.R.; Nepom, B.; Hutt-Fletcher, L.M. Epstein-Barr virus uses HLA class II as a cofactor for infection of B lymphocytes. J. Virol. 1997, 71, 4657–4662. [Google Scholar] [PubMed]
  17. Wang, X.; Kenyon, W.J.; Li, Q.; Mullberg, J.; Hutt-Fletcher, L.M. Epstein-Barr virus uses different complexes of glycoproteins gH and gL to infect B lymphocytes and epithelial cells. J. Virol. 1998, 72, 5552–5558. [Google Scholar] [PubMed]
  18. Chesnokova, L.S.; Nishimura, S.L.; Hutt-Fletcher, L.M. Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins alphavbeta6 or alphavbeta8. Proc. Natl. Acad. Sci. USA 2009, 106, 20464–20469. [Google Scholar] [CrossRef] [PubMed]
  19. Cesarman, E.; Chang, Y.; Moore, P.S.; Said, J.W.; Knowles, D.M. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N. Engl. J. Med. 1995, 332, 1186–1191. [Google Scholar] [CrossRef] [PubMed]
  20. Chang, Y.; Cesarman, E.; Pessin, M.S.; Lee, F.; Culpepper, J.; Knowles, D.M.; Moore, P.S. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994, 266, 1865–1869. [Google Scholar] [CrossRef] [PubMed]
  21. Soulier, J.; Grollet, L.; Oksenhendler, E.; Cacoub, P.; Cazals-Hatem, D.; Babinet, P.; d'Agay, M.F.; Clauvel, J.P.; Raphael, M.; Degos, L.; et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 1995, 86, 1276–1280. [Google Scholar] [PubMed]
  22. Morris, K. Cancer? In Africa? Lancet Oncol. 2003, 4, 5. [Google Scholar] [CrossRef] [PubMed]
  23. Parkin, D.M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics, 2002. CA: Cancer J. Clin. 2005, 55, 74–108. [Google Scholar] [CrossRef]
  24. Chadburn, A.; Abdul-Nabi, A.M.; Teruya, B.S.; Lo, A.A. Lymphoid proliferations associated with human immunodeficiency virus infection. Arch. Pathol. Lab. Med. 2013, 137, 360–370. [Google Scholar] [CrossRef] [PubMed]
  25. Sitas, F.; Newton, R. Kaposi's sarcoma in South Africa. J. Natl. Cancer Inst. Monogr. 2001, 28, 1–4. [Google Scholar] [PubMed]
  26. Dedicoat, M.; Newton, R.; Alkharsah, K.R.; Sheldon, J.; Szabados, I.; Ndlovu, B.; Page, T.; Casabonne, D.; Gilks, C.F.; Cassol, S.A.; et al. Mother-to-child transmission of human herpesvirus-8 in South Africa. J. Infect. Dis. 2004, 190, 1068–1075. [Google Scholar] [CrossRef] [PubMed]
  27. Henke-Gendo, C.; Schulz, T.F. Transmission and disease association of Kaposi's sarcoma-associated herpesvirus: Recent developments. Curr. Opin. Infect. Dis. 2004, 17, 53–57. [Google Scholar] [CrossRef] [PubMed]
  28. Matteoli, B.; Broccolo, F.; Scaccino, A.; Cottoni, F.; Angeloni, A.; Faggioni, A.; Ceccherini-Nelli, L. In vivo and in vitro evidence for an association between the route-specific transmission of HHV-8 and the virus genotype. J. Med. Virol. 2012, 84, 786–791. [Google Scholar] [CrossRef] [PubMed]
  29. Mbulaiteye, S.; Marshall, V.; Bagni, R.K.; Wang, C.D.; Mbisa, G.; Bakaki, P.M.; Owor, A.M.; Ndugwa, C.M.; Engels, E.A.; Katongole-Mbidde, E.; et al. Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host. J. Infect. Dis. 2006, 193, 1250–1257. [Google Scholar] [CrossRef] [PubMed]
  30. Vieira, J.; Huang, M.L.; Koelle, D.M.; Corey, L. Transmissible Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of men with a history of Kaposi's sarcoma. J. Virol. 1997, 71, 7083–7087. [Google Scholar] [PubMed]
  31. Koelle, D.M.; Huang, M.L.; Chandran, B.; Vieira, J.; Piepkorn, M.; Corey, L. Frequent detection of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: Clinical and immunologic correlates. J. Infect. Dis. 1997, 176, 94–102. [Google Scholar] [CrossRef] [PubMed]
  32. Veettil, M.V.; Bandyopadhyay, C.; Dutta, D.; Chandran, B. Interaction of KSHV with host cell surface receptors and cell entry. Viruses 2014, 6, 4024–4046. [Google Scholar] [CrossRef] [PubMed]
  33. Neipel, F.; Albrecht, J.C.; Fleckenstein, B. Human herpesvirus 8—The first human rhadinovirus. J. Natl. Cancer Inst. Monogr. 1998, 23, 73–77. [Google Scholar] [CrossRef] [PubMed]
  34. Chandran, B. Early events in Kaposi's sarcoma-associated herpesvirus infection of target cells. J. Virol. 2010, 84, 2188–2199. [Google Scholar] [CrossRef] [PubMed]
  35. Wang, F.Z.; Akula, S.M.; Sharma-Walia, N.; Zeng, L.; Chandran, B. Human herpesvirus 8 envelope glycoprotein B mediates cell adhesion via its RGD sequence. J. Virol. 2003, 77, 3131–3147. [Google Scholar] [CrossRef] [PubMed]
  36. Hahn, A.S.; Kaufmann, J.K.; Wies, E.; Naschberger, E.; Panteleev-Ivlev, J.; Schmidt, K.; Holzer, A.; Schmidt, M.; Chen, J.; Konig, S.; et al. The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus. Nat. Med. 2012, 18, 961–966. [Google Scholar] [CrossRef] [PubMed]
  37. Birkmann, A.; Mahr, K.; Ensser, A.; Yaguboglu, S.; Titgemeyer, F.; Fleckenstein, B.; Neipel, F. Cell surface heparan sulfate is a receptor for human herpesvirus 8 and interacts with envelope glycoprotein K8.1. J. Virol. 2001, 75, 11583–11593. [Google Scholar] [CrossRef] [PubMed]
  38. Akula, S.M.; Pramod, N.P.; Wang, F.Z.; Chandran, B. Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties. Virology 2001, 284, 235–249. [Google Scholar] [CrossRef] [PubMed]
  39. Veettil, M.V.; Sadagopan, S.; Sharma-Walia, N.; Wang, F.Z.; Raghu, H.; Varga, L.; Chandran, B. Kaposi's sarcoma-associated herpesvirus forms a multimolecular complex of integrins (alphavbeta5, alphavbeta3, and alpha3beta1) and CD98-xCT during infection of human dermal microvascular endothelial cells, and CD98-xCT is essential for the postentry stage of infection. J. Virol. 2008, 82, 12126–12144. [Google Scholar] [CrossRef] [PubMed]
  40. Akula, S.M.; Pramod, N.P.; Wang, F.Z.; Chandran, B. Integrin alpha3beta1 (CD 49c/29) is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Cell 2002, 108, 407–419. [Google Scholar] [CrossRef] [PubMed]
  41. Walker, L.R.; Hussein, H.A.; Akula, S.M. Disintegrin-like domain of glycoprotein B regulates Kaposi's sarcoma-associated herpesvirus infection of cells. J. Gen. Virol. 2014, 95, 1770–1782. [Google Scholar] [CrossRef] [PubMed]
  42. Kaleeba, J.A.; Berger, E.A. Kaposi's sarcoma-associated herpesvirus fusion-entry receptor: Cystine transporter xCT. Science 2006, 311, 1921–1924. [Google Scholar] [CrossRef] [PubMed]
  43. Rappocciolo, G.; Hensler, H.R.; Jais, M.; Reinhart, T.A.; Pegu, A.; Jenkins, F.J.; Rinaldo, C.R. Human herpesvirus 8 infects and replicates in primary cultures of activated B lymphocytes through DC-SIGN. J. Virol. 2008, 82, 4793–4806. [Google Scholar] [CrossRef] [PubMed]
  44. Rappocciolo, G.; Jenkins, F.J.; Hensler, H.R.; Piazza, P.; Jais, M.; Borowski, L.; Watkins, S.C.; Rinaldo, C.R., Jr. DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. J. Immunol. 2006, 176, 1741–1749. [Google Scholar] [CrossRef] [PubMed]
  45. Hensler, H.R.; Tomaszewski, M.J.; Rappocciolo, G.; Rinaldo, C.R.; Jenkins, F.J. Human herpesvirus 8 glycoprotein B binds the entry receptor DC-SIGN. Virus Res. 2014, 190, 97–103. [Google Scholar] [CrossRef] [PubMed]
  46. Chakraborty, S.; Veettil, M.V.; Bottero, V.; Chandran, B. Kaposi's sarcoma-associated herpesvirus interacts with EphrinA2 receptor to amplify signaling essential for productive infection. Proc. Natl. Acad. Sci. USA 2012, 109, E1163–E1172. [Google Scholar] [CrossRef] [PubMed]
  47. Dutta, D.; Chakraborty, S.; Bandyopadhyay, C.; Valiya Veettil, M.; Ansari, M.A.; Singh, V.V.; Chandran, B. EphrinA2 regulates clathrin mediated KSHV endocytosis in fibroblast cells by coordinating integrin-associated signaling and c-Cbl directed polyubiquitination. PLoS Pathog. 2013, 9, e1003510. [Google Scholar] [CrossRef] [PubMed]
  48. Raghu, H.; Sharma-Walia, N.; Veettil, M.V.; Sadagopan, S.; Chandran, B. Kaposi's sarcoma-associated herpesvirus utilizes an actin polymerization-dependent macropinocytic pathway to enter human dermal microvascular endothelial and human umbilical vein endothelial cells. J. Virol. 2009, 83, 4895–4911. [Google Scholar] [CrossRef] [PubMed]
  49. Akula, S.M.; Naranatt, P.P.; Walia, N.S.; Wang, F.Z.; Fegley, B.; Chandran, B. Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) infection of human fibroblast cells occurs through endocytosis. J. Virol. 2003, 77, 7978–7990. [Google Scholar] [CrossRef] [PubMed]
  50. Krishnan, H.H.; Sharma-Walia, N.; Streblow, D.N.; Naranatt, P.P.; Chandran, B. Focal adhesion kinase is critical for entry of Kaposi's sarcoma-associated herpesvirus into target cells. J. Virol. 2006, 80, 1167–1180. [Google Scholar] [CrossRef] [PubMed]
  51. Veettil, M.V.; Sharma-Walia, N.; Sadagopan, S.; Raghu, H.; Sivakumar, R.; Naranatt, P.P.; Chandran, B. RhoA-GTPase facilitates entry of Kaposi's sarcoma-associated herpesvirus into adherent target cells in a Src-dependent manner. J. Virol. 2006, 80, 11432–11446. [Google Scholar] [CrossRef] [PubMed]
  52. Naranatt, P.P.; Akula, S.M.; Zien, C.A.; Krishnan, H.H.; Chandran, B. Kaposi's sarcoma-associated herpesvirus induces the phosphatidylinositol 3-kinase-PKC-zeta-MEK-ERK signaling pathway in target cells early during infection: Implications for infectivity. J. Virol. 2003, 77, 1524–1539. [Google Scholar] [CrossRef] [PubMed]
  53. de Villiers, E.M.; Fauquet, C.; Broker, T.R.; Bernard, H.U.; zur Hausen, H. Classification of papillomaviruses. Virology 2004, 324, 17–27. [Google Scholar] [CrossRef] [PubMed]
  54. Trottier, H.; Franco, E.L. The epidemiology of genital human papillomavirus infection. Vaccine 2006, 24 Suppl 1, S1–S15. [Google Scholar] [CrossRef] [PubMed]
  55. Pyeon, D.; Pearce, S.M.; Lank, S.M.; Ahlquist, P.; Lambert, P.F. Establishment of human papillomavirus infection requires cell cycle progression. PLoS Pathog. 2009, 5, e1000318. [Google Scholar] [CrossRef] [PubMed]
  56. Schiller, J.T.; Day, P.M.; Kines, R.C. Current understanding of the mechanism of HPV infection. Gynecol. Oncol. 2010, 118, S12–S17. [Google Scholar] [CrossRef] [PubMed]
  57. Buck, C.B.; Cheng, N.; Thompson, C.D.; Lowy, D.R.; Steven, A.C.; Schiller, J.T.; Trus, B.L. Arrangement of L2 within the papillomavirus capsid. J. Virol. 2008, 82, 5190–5197. [Google Scholar] [CrossRef] [PubMed]
  58. Raff, A.B.; Woodham, A.W.; Raff, L.M.; Skeate, J.G.; Yan, L.; Da Silva, D.M.; Schelhaas, M.; Kast, W.M. The evolving field of human papillomavirus receptor research: A review of binding and entry. J. Virol. 2013, 87, 6062–6072. [Google Scholar] [CrossRef] [PubMed]
  59. Kines, R.C.; Thompson, C.D.; Lowy, D.R.; Schiller, J.T.; Day, P.M. The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. Proc. Natl. Acad. Sci. USA 2009, 106, 20458–20463. [Google Scholar] [CrossRef] [PubMed]
  60. Abban, C.Y.; Meneses, P.I. Usage of heparan sulfate, integrins, and FAK in HPV16 infection. Virology 2010, 403, 1–16. [Google Scholar] [CrossRef] [PubMed]
  61. Johnson, K.M.; Kines, R.C.; Roberts, J.N.; Lowy, D.R.; Schiller, J.T.; Day, P.M. Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. J. Virol. 2009, 83, 2067–2074. [Google Scholar] [CrossRef] [PubMed]
  62. Culp, T.D.; Budgeon, L.R.; Christensen, N.D. Human papillomaviruses bind a basal extracellular matrix component secreted by keratinocytes which is distinct from a membrane-associated receptor. Virology 2006, 347, 147–159. [Google Scholar] [CrossRef] [PubMed]
  63. Schäfer, G.; Kabanda, S.; van Rooyen, B.; Marusic, M.B.; Banks, L.; Parker, M.I. The role of inflammation in HPV infection of the oesophagus. BMC Cancer 2013, 13, e185. [Google Scholar] [CrossRef] [Green Version]
  64. Selinka, H.C.; Florin, L.; Patel, H.D.; Freitag, K.; Schmidtke, M.; Makarov, V.A.; Sapp, M. Inhibition of transfer to secondary receptors by heparan sulfate-binding drug or antibody induces noninfectious uptake of human papillomavirus. J. Virol. 2007, 81, 10970–10980. [Google Scholar] [CrossRef] [PubMed]
  65. Shafti-Keramat, S.; Handisurya, A.; Kriehuber, E.; Meneguzzi, G.; Slupetzky, K.; Kirnbauer, R. Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. J. Virol. 2003, 77, 13125–13135. [Google Scholar] [CrossRef] [PubMed]
  66. Culp, T.D.; Budgeon, L.R.; Marinkovich, M.P.; Meneguzzi, G.; Christensen, N.D. Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells. J. Virol. 2006, 80, 8940–8950. [Google Scholar] [CrossRef] [PubMed]
  67. Richards, K.F.; Bienkowska-Haba, M.; Dasgupta, J.; Chen, X.S.; Sapp, M. Multiple heparan sulfate binding site engagements are required for the infectious entry of human papillomavirus type 16. J. Virol. 2013, 87, 11426–11437. [Google Scholar] [CrossRef] [PubMed]
  68. Bienkowska-Haba, M.; Patel, H.D.; Sapp, M. Target cell cyclophilins facilitate human papillomavirus type 16 infection. PLoS Pathog. 2009, 5, e1000524. [Google Scholar] [CrossRef] [PubMed]
  69. Day, P.M.; Schiller, J.T. The role of furin in papillomavirus infection. Futur. Microbiol. 2009, 4, 1255–1262. [Google Scholar] [CrossRef]
  70. Richards, R.M.; Lowy, D.R.; Schiller, J.T.; Day, P.M. Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc. Natl. Acad. Sci. USA 2006, 103, 1522–1527. [Google Scholar] [CrossRef] [PubMed]
  71. Evander, M.; Frazer, I.H.; Payne, E.; Qi, Y.M.; Hengst, K.; McMillan, N.A. Identification of the alpha6 integrin as a candidate receptor for papillomaviruses. J. Virol. 1997, 71, 2449–2456. [Google Scholar] [PubMed]
  72. Yoon, C.S.; Kim, K.D.; Park, S.N.; Cheong, S.W. Alpha(6) integrin is the main receptor of human papillomavirus type 16 VLP. Biochem. Biophys. Res. Commun. 2001, 283, 668–673. [Google Scholar] [CrossRef] [PubMed]
  73. Surviladze, Z.; Dziduszko, A.; Ozbun, M.A. Essential roles for soluble virion-associated heparan sulfonated proteoglycans and growth factors in human papillomavirus infections. PLoS Pathog. 2012, 8, e1002519. [Google Scholar] [CrossRef] [PubMed]
  74. Spoden, G.; Freitag, K.; Husmann, M.; Boller, K.; Sapp, M.; Lambert, C.; Florin, L. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs). PLoS ONE 2008, 3, e3313. [Google Scholar] [CrossRef] [PubMed]
  75. Scheffer, K.D.; Gawlitza, A.; Spoden, G.A.; Zhang, X.A.; Lambert, C.; Berditchevski, F.; Florin, L. Tetraspanin CD151 mediates papillomavirus type 16 endocytosis. J. Virol. 2013, 87, 3435–3446. [Google Scholar] [CrossRef] [PubMed]
  76. Hitchcock, J.K.; Katz, A.A.; Schäfer, G. Dynamic reciprocity: The role of annexin A2 in tissue integrity. J. Cell Commun. Signal. 2014, 8, 125–133. [Google Scholar] [CrossRef] [PubMed]
  77. Woodham, A.W.; Da Silva, D.M.; Skeate, J.G.; Raff, A.B.; Ambroso, M.R.; Brand, H.E.; Isas, J.M.; Langen, R.; Kast, W.M. The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection. PLoS ONE 2012, 7, e43519. [Google Scholar] [CrossRef] [PubMed]
  78. Dziduszko, A.; Ozbun, M.A. Annexin A2 and S100A10 regulate human papillomavirus type 16 entry and intracellular trafficking in human keratinocytes. J. Virol. 2013, 87, 7502–7515. [Google Scholar] [CrossRef] [PubMed]
  79. Schelhaas, M.; Shah, B.; Holzer, M.; Blattmann, P.; Kuhling, L.; Day, P.M.; Schiller, J.T.; Helenius, A. Entry of human papillomavirus type 16 by actin-dependent, clathrin- and lipid raft-independent endocytosis. PLoS Pathog. 2012, 8, e1002657. [Google Scholar] [CrossRef] [PubMed]
  80. Surviladze, Z.; Sterk, R.T.; DeHaro, S.A.; Ozbun, M.A. Cellular entry of human papillomavirus type 16 involves activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway and inhibition of autophagy. J. Virol. 2013, 87, 2508–2517. [Google Scholar] [CrossRef] [PubMed]
  81. Compton, T. Receptors and immune sensors: The complex entry path of human cytomegalovirus. Trends Cell Biol. 2004, 14, 5–8. [Google Scholar] [CrossRef] [PubMed]
  82. Blanchard, E.; Belouzard, S.; Goueslain, L.; Wakita, T.; Dubuisson, J.; Wychowski, C.; Rouille, Y. Hepatitis C Virus entry depends on clathrin-mediated endocytosis. J. Virol. 2006, 80, 6964–6972. [Google Scholar] [CrossRef] [PubMed]
  83. Brazzoli, M.; Bianchi, A.; Filippini, S.; Weiner, A.; Zhu, Q.; Pizza, M.; Crotta, S. CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes. J. Virol. 2008, 82, 8316–8329. [Google Scholar] [CrossRef] [PubMed]
  84. Farquhar, M.J.; Hu, K.; Harris, H.J.; Davis, C.; Brimacombe, C.L.; Fletcher, S.J.; Baumert, T.F.; Rappoport, J.Z.; Balfe, P.; McKeating, J.A. Hepatitis C Virus induces CD81 and claudin-1 endocytosis. J. Virol. 2012, 86, 4305–4316. [Google Scholar] [CrossRef] [PubMed]
  85. Lupberger, J.; Zeisel, M.B.; Xiao, F.; Thumann, C.; Fofana, I.; Zona, L.; Davis, C.; Mee, C.J.; Turek, M.; Gorke, S.; et al. EGFR and EphA2 are host factors for Hepatitis C Virus entry and possible targets for antiviral therapy. Nat. Med. 2011, 17, 589–595. [Google Scholar] [CrossRef] [PubMed]
  86. Zona, L.; Lupberger, J.; Sidahmed-Adrar, N.; Thumann, C.; Harris, H.J.; Barnes, A.; Florentin, J.; Tawar, R.G.; Xiao, F.; Turek, M.; et al. HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex. Cell Host Microbe 2013, 13, 302–313. [Google Scholar] [CrossRef] [PubMed]
  87. Richards, K.F.; Mukherjee, S.; Bienkowska-Haba, M.; Pang, J.; Sapp, M. Human papillomavirus species-specific interaction with the basement membrane-resident non-heparan sulfate receptor. Viruses 2014, 6, 4856–4879. [Google Scholar] [CrossRef] [PubMed]
  88. Johne, R.; Buck, C.B.; Allander, T.; Atwood, W.J.; Garcea, R.L.; Imperiale, M.J.; Major, E.O.; Ramqvist, T.; Norkin, L.C. Taxonomical developments in the family polyomaviridae. Arch. Virol. 2011, 156, 1627–1634. [Google Scholar] [CrossRef] [PubMed]
  89. Spurgeon, M.E.; Lambert, P.F. Merkel cell polyomavirus: A newly discovered human virus with oncogenic potential. Virology 2013, 435, 118–130. [Google Scholar] [CrossRef] [PubMed]
  90. Kaae, J.; Hansen, A.V.; Biggar, R.J.; Boyd, H.A.; Moore, P.S.; Wohlfahrt, J.; Melbye, M. Merkel cell carcinoma: Incidence, mortality, and risk of other cancers. J. Natl. Cancer Inst. 2010, 102, 793–801. [Google Scholar] [CrossRef] [PubMed]
  91. Feng, H.; Shuda, M.; Chang, Y.; Moore, P.S. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319, 1096–1100. [Google Scholar] [CrossRef] [PubMed]
  92. Feng, H.; Taylor, J.L.; Benos, P.V.; Newton, R.; Waddell, K.; Lucas, S.B.; Chang, Y.; Moore, P.S. Human transcriptome subtraction by using short sequence tags to search for tumor viruses in conjunctival carcinoma. J. Virol. 2007, 81, 11332–11340. [Google Scholar] [CrossRef] [PubMed]
  93. Houben, R.; Shuda, M.; Weinkam, R.; Schrama, D.; Feng, H.; Chang, Y.; Moore, P.S.; Becker, J.C. Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens. J. Virol. 2010, 84, 7064–7072. [Google Scholar] [CrossRef] [PubMed]
  94. Shuda, M.; Arora, R.; Kwun, H.J.; Feng, H.; Sarid, R.; Fernandez-Figueras, M.T.; Tolstov, Y.; Gjoerup, O.; Mansukhani, M.M.; Swerdlow, S.H.; et al. Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int. J. Cancer. J. Int. Cancer 2009, 125, 1243–1249. [Google Scholar] [CrossRef]
  95. Shuda, M.; Kwun, H.J.; Feng, H.; Chang, Y.; Moore, P.S. Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. J. Clin. Investig. 2011, 121, 3623–3634. [Google Scholar] [CrossRef] [PubMed]
  96. Andres, C.; Belloni, B.; Puchta, U.; Sander, C.A.; Flaig, M.J. Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors. J. Cutan. Pathol. 2010, 37, 28–34. [Google Scholar] [CrossRef] [PubMed]
  97. Becker, J.C.; Houben, R.; Ugurel, S.; Trefzer, U.; Pfohler, C.; Schrama, D. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J. Investig. Dermatol. 2009, 129, 248–250. [Google Scholar] [CrossRef] [PubMed]
  98. Kassem, A.; Schopflin, A.; Diaz, C.; Weyers, W.; Stickeler, E.; Werner, M.; Zur Hausen, A. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res. 2008, 68, 5009–5013. [Google Scholar] [CrossRef] [PubMed]
  99. Wieland, U.; Mauch, C.; Kreuter, A.; Krieg, T.; Pfister, H. Merkel cell polyomavirus DNA in persons without Merkel cell carcinoma. Emerg. Infect. Dis. 2009, 15, 1496–1498. [Google Scholar] [CrossRef] [PubMed]
  100. Laude, H.C.; Jonchere, B.; Maubec, E.; Carlotti, A.; Marinho, E.; Couturaud, B.; Peter, M.; Sastre-Garau, X.; Avril, M.F.; Dupin, N.; et al. Distinct Merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with Merkel cell carcinoma. PLoS Pathog. 2010, 6, e1001076. [Google Scholar] [CrossRef] [PubMed]
  101. Agelli, M.; Clegg, L.X. Epidemiology of primary Merkel cell carcinoma in the United States. J. Am. Acad. Dermatol. 2003, 49, 832–841. [Google Scholar] [CrossRef] [PubMed]
  102. Engels, E.A.; Frisch, M.; Goedert, J.J.; Biggar, R.J.; Miller, R.W. Merkel cell carcinoma and HIV infection. Lancet 2002, 359, 497–498. [Google Scholar] [CrossRef] [PubMed]
  103. Schowalter, R.M.; Pastrana, D.V.; Pumphrey, K.A.; Moyer, A.L.; Buck, C.B. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 2010, 7, 509–515. [Google Scholar] [CrossRef] [PubMed]
  104. Tolstov, Y.L.; Pastrana, D.V.; Feng, H.; Becker, J.C.; Jenkins, F.J.; Moschos, S.; Chang, Y.; Buck, C.B.; Moore, P.S. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int. J. Cancer. J. Int. Cancer 2009, 125, 1250–1256. [Google Scholar] [CrossRef]
  105. van der Meijden, E.; Bialasiewicz, S.; Rockett, R.J.; Tozer, S.J.; Sloots, T.P.; Feltkamp, M.C. Different serologic behavior of MCPyV, TSPyV, HPyV6, HPyV7 and HPyV9 polyomaviruses found on the skin. PLoS ONE 2013, 8, e81078. [Google Scholar] [CrossRef] [PubMed]
  106. Martel-Jantin, C.; Pedergnana, V.; Nicol, J.T.; Leblond, V.; Tregouet, D.A.; Tortevoye, P.; Plancoulaine, S.; Coursaget, P.; Touze, A.; Abel, L.; et al. Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings. J. Clin. Virol. Off. Publ. Pan Am. Soc. Clin. Virol. 2013, 58, 288–291. [Google Scholar] [CrossRef]
  107. Matsushita, M.; Kuwamoto, S.; Iwasaki, T.; Higaki-Mori, H.; Yashima, S.; Kato, M.; Murakami, I.; Horie, Y.; Kitamura, Y.; Hayashi, K. Detection of Merkel cell polyomavirus in the human tissues from 41 Japanese autopsy cases using polymerase chain reaction. Intervirology 2013, 56, 1–5. [Google Scholar] [CrossRef] [PubMed]
  108. Loyo, M.; Guerrero-Preston, R.; Brait, M.; Hoque, M.O.; Chuang, A.; Kim, M.S.; Sharma, R.; Liegeois, N.J.; Koch, W.M.; Califano, J.A.; et al. Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission. Int. J. Cancer. J. Int. Cancer 2010, 126, 2991–2996. [Google Scholar]
  109. Zur Hausen, A.; Rennspiess, D.; Winnepenninckx, V.; Speel, E.J.; Kurz, A.K. Early B-cell differentiation in Merkel cell carcinomas: Clues to cellular ancestry. Cancer Res. 2013, 73, 4982–4987. [Google Scholar] [CrossRef] [PubMed]
  110. Jankowski, M.; Kopinski, P.; Schwartz, R.; Czajkowski, R. Merkel cell carcinoma: Is this a true carcinoma? Exp. Dermatol. 2014, 23, 792–794. [Google Scholar] [CrossRef] [PubMed]
  111. Schowalter, R.M.; Buck, C.B. The Merkel cell polyomavirus minor capsid protein. PLoS Pathogens 2013, 9, e1003558. [Google Scholar] [CrossRef] [PubMed]
  112. Neu, U.; Hengel, H.; Blaum, B.S.; Schowalter, R.M.; Macejak, D.; Gilbert, M.; Wakarchuk, W.W.; Imamura, A.; Ando, H.; Kiso, M.; et al. Structures of Merkel cell polyomavirus VP1 complexes define a sialic acid binding site required for infection. PLoS Pathogens 2012, 8, e1002738. [Google Scholar] [CrossRef] [PubMed]
  113. Schowalter, R.M.; Pastrana, D.V.; Buck, C.B. Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry. PLoS Pathogens 2011, 7, e1002161. [Google Scholar] [CrossRef] [PubMed]
  114. Campanero-Rhodes, M.A.; Smith, A.; Chai, W.; Sonnino, S.; Mauri, L.; Childs, R.A.; Zhang, Y.; Ewers, H.; Helenius, A.; Imberty, A.; et al. N-glycolyl GM1 ganglioside as a receptor for simian virus 40. J. Virol. 2007, 81, 12846–12858. [Google Scholar] [CrossRef] [PubMed]
  115. Low, J.A.; Magnuson, B.; Tsai, B.; Imperiale, M.J. Identification of gangliosides GD1b and GT1b as receptors for BK virus. J. Virol. 2006, 80, 1361–1366. [Google Scholar] [CrossRef] [PubMed]
  116. Smith, A.E.; Lilie, H.; Helenius, A. Ganglioside-dependent cell attachment and endocytosis of murine polyomavirus-like particles. FEBS Lett. 2003, 555, 199–203. [Google Scholar] [CrossRef] [PubMed]
  117. Tsai, B.; Gilbert, J.M.; Stehle, T.; Lencer, W.; Benjamin, T.L.; Rapoport, T.A. Gangliosides are receptors for murine polyoma virus and SV40. EMBO J. 2003, 22, 4346–4355. [Google Scholar] [CrossRef] [PubMed]
  118. Erickson, K.D.; Garcea, R.L.; Tsai, B. Ganglioside GT1b is a putative host cell receptor for the Merkel cell polyomavirus. J. Virol. 2009, 83, 10275–10279. [Google Scholar] [CrossRef] [PubMed]
  119. Schowalter, R.M.; Reinhold, W.C.; Buck, C.B. Entry tropism of BK and Merkel cell polyomaviruses in cell culture. PLoS ONE 2012, 7, e42181. [Google Scholar] [CrossRef] [PubMed]
  120. Gust, I.D.; Burrell, C.J.; Coulepis, A.G.; Robinson, W.S.; Zuckerman, A.J. Taxonomic classification of human hepatitis B virus. Intervirology 1986, 25, 14–29. [Google Scholar] [CrossRef] [PubMed]
  121. Seeger, C.; Mason, W.S. Hepatitis B virus biology. Microbiol. Mol. Biol. Rev. MMBR 2000, 64, 51–68. [Google Scholar] [CrossRef]
  122. El-Serag, H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012, 142, 1264–1273.e1. [Google Scholar] [CrossRef] [PubMed]
  123. Seitz, S.; Urban, S.; Antoni, C.; Bottcher, B. Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions. EMBO J. 2007, 26, 4160–4167. [Google Scholar] [CrossRef] [PubMed]
  124. Wynne, S.A.; Crowther, R.A.; Leslie, A.G. The crystal structure of the human hepatitis B virus capsid. Mol. Cell 1999, 3, 771–780. [Google Scholar] [CrossRef] [PubMed]
  125. Gavilanes, F.; Gonzalez-Ros, J.M.; Peterson, D.L. Structure of hepatitis B surface antigen. Characterization of the lipid components and their association with the viral proteins. J. Biol. Chem. 1982, 257, 7770–7777. [Google Scholar] [PubMed]
  126. Heermann, K.H.; Goldmann, U.; Schwartz, W.; Seyffarth, T.; Baumgarten, H.; Gerlich, W.H. Large surface proteins of hepatitis B virus containing the pre-s sequence. J. Virol. 1984, 52, 396–402. [Google Scholar] [PubMed]
  127. Bruss, V.; Hagelstein, J.; Gerhardt, E.; Galle, P.R. Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity. Virology 1996, 218, 396–399. [Google Scholar] [CrossRef] [PubMed]
  128. Gripon, P.; Cannie, I.; Urban, S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J. Virol. 2005, 79, 1613–1622. [Google Scholar] [CrossRef] [PubMed]
  129. Gripon, P.; Le Seyec, J.; Rumin, S.; Guguen-Guillouzo, C. Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity. Virology 1995, 213, 292–299. [Google Scholar] [CrossRef] [PubMed]
  130. Gripon, P.; Diot, C.; Theze, N.; Fourel, I.; Loreal, O.; Brechot, C.; Guguen-Guillouzo, C. Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. J. Virol. 1988, 62, 4136–4143. [Google Scholar] [PubMed]
  131. Gripon, P.; Rumin, S.; Urban, S.; Le Seyec, J.; Glaise, D.; Cannie, I.; Guyomard, C.; Lucas, J.; Trepo, C.; Guguen-Guillouzo, C. Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. USA 2002, 99, 15655–15660. [Google Scholar] [CrossRef] [PubMed]
  132. Kock, J.; Nassal, M.; MacNelly, S.; Baumert, T.F.; Blum, H.E.; von Weizsacker, F. Efficient infection of primary tupaia hepatocytes with purified human and woolly monkey hepatitis B virus. J. Virol. 2001, 75, 5084–5089. [Google Scholar] [CrossRef] [PubMed]
  133. Walter, E.; Keist, R.; Niederost, B.; Pult, I.; Blum, H.E. Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo. Hepatology 1996, 24, 1–5. [Google Scholar] [PubMed]
  134. Zahn, A.; Allain, J.P. Hepatitis C virus and hepatitis B virus bind to heparin: Purification of largely IgG-free virions from infected plasma by heparin chromatography. J. Gen. Virol. 2005, 86, 677–685. [Google Scholar] [CrossRef] [PubMed]
  135. Leistner, C.M.; Gruen-Bernhard, S.; Glebe, D. Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell. Microbiol. 2008, 10, 122–133. [Google Scholar] [PubMed]
  136. Barth, H.; Schafer, C.; Adah, M.I.; Zhang, F.; Linhardt, R.J.; Toyoda, H.; Kinoshita-Toyoda, A.; Toida, T.; Van Kuppevelt, T.H.; Depla, E.; et al. Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J. Biol. Chem. 2003, 278, 41003–41012. [Google Scholar] [CrossRef] [PubMed]
  137. Chen, Y.; Maguire, T.; Hileman, R.E.; Fromm, J.R.; Esko, J.D.; Linhardt, R.J.; Marks, R.M. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat. Med. 1997, 3, 866–871. [Google Scholar] [CrossRef] [PubMed]
  138. Rathore, D.; McCutchan, T.F.; Garboczi, D.N.; Toida, T.; Hernaiz, M.J.; LeBrun, L.A.; Lang, S.C.; Linhardt, R.J. Direct measurement of the interactions of glycosaminoglycans and a heparin decasaccharide with the malaria circumsporozoite protein. Biochemistry 2001, 40, 11518–11524. [Google Scholar] [CrossRef] [PubMed]
  139. Yan, H.; Zhong, G.; Xu, G.; He, W.; Jing, Z.; Gao, Z.; Huang, Y.; Qi, Y.; Peng, B.; Wang, H.; et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 2012, 1, e00049. [Google Scholar] [CrossRef] [PubMed]
  140. Ni, Y.; Lempp, F.A.; Mehrle, S.; Nkongolo, S.; Kaufman, C.; Falth, M.; Stindt, J.; Koniger, C.; Nassal, M.; Kubitz, R.; et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology 2014, 146, 1070–1083. [Google Scholar] [CrossRef] [PubMed]
  141. Zhong, G.; Yan, H.; Wang, H.; He, W.; Jing, Z.; Qi, Y.; Fu, L.; Gao, Z.; Huang, Y.; Xu, G.; et al. Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of tupaia hepatocytes. J. Virol. 2013, 87, 7176–7184. [Google Scholar] [CrossRef] [PubMed]
  142. Huang, H.C.; Chen, C.C.; Chang, W.C.; Tao, M.H.; Huang, C. Entry of hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent endocytosis. J. Virol. 2012, 86, 9443–9453. [Google Scholar] [CrossRef] [PubMed]
  143. Stross, C.; Kluge, S.; Weissenberger, K.; Winands, E.; Haussinger, D.; Kubitz, R. A dileucine motif is involved in plasma membrane expression and endocytosis of rat sodium taurocholate cotransporting polypeptide (NTCP). Am. J. Physiol. Gastrointest. Liver Physiol. 2013, 305, G722–G730. [Google Scholar] [CrossRef] [PubMed]
  144. Morgan, R.L.; Baack, B.; Smith, B.D.; Yartel, A.; Pitasi, M.; Falck-Ytter, Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: A meta-analysis of observational studies. Ann. Intern. Med. 2013, 158, 329–337. [Google Scholar] [CrossRef] [PubMed]
  145. Tang, H.; Grise, H. Cellular and molecular biology of HCV infection and hepatitis. Clin. Sci. 2009, 117, 49–65. [Google Scholar] [CrossRef] [PubMed]
  146. Shepard, C.W.; Finelli, L.; Alter, M.J. Global epidemiology of hepatitis C virus infection. Lancet Infect. Dis. 2005, 5, 558–567. [Google Scholar] [CrossRef] [PubMed]
  147. Brimacombe, C.L.; Grove, J.; Meredith, L.W.; Hu, K.; Syder, A.J.; Flores, M.V.; Timpe, J.M.; Krieger, S.E.; Baumert, T.F.; Tellinghuisen, T.L.; et al. Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. J. Virol. 2011, 85, 596–605. [Google Scholar] [CrossRef] [PubMed]
  148. Catanese, M.T.; Uryu, K.; Kopp, M.; Edwards, T.J.; Andrus, L.; Rice, W.J.; Silvestry, M.; Kuhn, R.J.; Rice, C.M. Ultrastructural analysis of hepatitis C virus particles. Proc. Natl. Acad. Sci. USA 2013, 110, 9505–9510. [Google Scholar] [CrossRef] [PubMed]
  149. Merz, A.; Long, G.; Hiet, M.S.; Brugger, B.; Chlanda, P.; Andre, P.; Wieland, F.; Krijnse-Locker, J.; Bartenschlager, R. Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J. Biol. Chem. 2011, 286, 3018–3032. [Google Scholar] [CrossRef] [PubMed]
  150. Jiang, J.; Cun, W.; Wu, X.; Shi, Q.; Tang, H.; Luo, G. Hepatitis C virus attachment mediated by apolipoprotein E binding to cell surface heparan sulfate. J. Virol. 2012, 86, 7256–7267. [Google Scholar] [CrossRef] [PubMed]
  151. Da Costa, D.; Turek, M.; Felmlee, D.J.; Girardi, E.; Pfeffer, S.; Long, G.; Bartenschlager, R.; Zeisel, M.B.; Baumert, T.F. Reconstitution of the entire hepatitis C virus life cycle in nonhepatic cells. J. Virol. 2012, 86, 11919–11925. [Google Scholar] [CrossRef] [PubMed]
  152. Baumert, T.F.; Meredith, L.; Ni, Y.; Felmlee, D.J.; McKeating, J.A.; Urban, S. Entry of hepatitis B and C viruses - recent progress and future impact. Curr. Opin. Virol. 2014, 4, 58–65. [Google Scholar] [CrossRef] [PubMed]
  153. Meredith, L.W.; Wilson, G.K.; Fletcher, N.F.; McKeating, J.A. Hepatitis C virus entry: Beyond receptors. Rev. Med. Virol. 2012, 22, 182–193. [Google Scholar] [CrossRef] [PubMed]
  154. Catanese, M.T.; Graziani, R.; von Hahn, T.; Moreau, M.; Huby, T.; Paonessa, G.; Santini, C.; Luzzago, A.; Rice, C.M.; Cortese, R.; et al. High-avidity monoclonal antibodies against the human scavenger class B type I receptor efficiently block hepatitis C virus infection in the presence of high-density lipoprotein. J. Virol. 2007, 81, 8063–8071. [Google Scholar] [CrossRef] [PubMed]
  155. Voisset, C.; Callens, N.; Blanchard, E.; Op De Beeck, A.; Dubuisson, J.; Vu-Dac, N. High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I. J. Biol. Chem. 2005, 280, 7793–7799. [Google Scholar] [CrossRef] [PubMed]
  156. Acton, S.; Rigotti, A.; Landschulz, K.T.; Xu, S.; Hobbs, H.H.; Krieger, M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996, 271, 518–520. [Google Scholar] [CrossRef] [PubMed]
  157. Schäfer, G.; Guler, R.; Murray, G.; Brombacher, F.; Brown, G.D. The role of scavenger receptor B1 in infection with mycobacterium tuberculosis in a murine model. PLoS ONE 2009, 4, e8448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  158. Rodrigues, C.D.; Hannus, M.; Prudencio, M.; Martin, C.; Goncalves, L.A.; Portugal, S.; Epiphanio, S.; Akinc, A.; Hadwiger, P.; Jahn-Hofmann, K.; et al. Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection. Cell Host Microbe 2008, 4, 271–282. [Google Scholar] [CrossRef] [PubMed]
  159. Evans, M.J.; von Hahn, T.; Tscherne, D.M.; Syder, A.J.; Panis, M.; Wolk, B.; Hatziioannou, T.; McKeating, J.A.; Bieniasz, P.D.; Rice, C.M. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007, 446, 801–805. [Google Scholar] [CrossRef] [PubMed]
  160. Davis, C.; Harris, H.J.; Hu, K.; Drummer, H.E.; McKeating, J.A.; Mullins, J.G.; Balfe, P. In silico directed mutagenesis identifies the CD81/claudin-1 hepatitis C virus receptor interface. Cell. Microbiol. 2012, 14, 1892–1903. [Google Scholar] [CrossRef] [PubMed]
  161. Sharma, N.R.; Mateu, G.; Dreux, M.; Grakoui, A.; Cosset, F.L.; Melikyan, G.B. Hepatitis C virus is primed by CD81 protein for low pH-dependent fusion. J. Biol. Chem. 2011, 286, 30361–30376. [Google Scholar] [CrossRef] [PubMed]
  162. Benedicto, I.; Molina-Jimenez, F.; Bartosch, B.; Cosset, F.L.; Lavillette, D.; Prieto, J.; Moreno-Otero, R.; Valenzuela-Fernandez, A.; Aldabe, R.; Lopez-Cabrera, M.; et al. The tight junction-associated protein occludin is required for a postbinding step in hepatitis C virus entry and infection. J. Virol. 2009, 83, 8012–8020. [Google Scholar] [CrossRef] [PubMed]
  163. Liu, S.; Yang, W.; Shen, L.; Turner, J.R.; Coyne, C.B.; Wang, T. Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J. Virol. 2009, 83, 2011–2014. [Google Scholar] [CrossRef] [PubMed]
  164. Ploss, A.; Evans, M.J.; Gaysinskaya, V.A.; Panis, M.; You, H.; de Jong, Y.P.; Rice, C.M. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 2009, 457, 882–886. [Google Scholar] [CrossRef] [PubMed]
  165. Sainz, B., Jr.; Barretto, N.; Martin, D.N.; Hiraga, N.; Imamura, M.; Hussain, S.; Marsh, K.A.; Yu, X.; Chayama, K.; Alrefai, W.A.; et al. Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat. Med. 2012, 18, 281–285. [Google Scholar] [CrossRef] [PubMed]
  166. Martin, D.N.; Uprichard, S.L. Identification of transferrin receptor 1 as a hepatitis C virus entry factor. Proc. Natl. Acad. Sci. USA 2013, 110, 10777–10782. [Google Scholar] [CrossRef] [PubMed]
  167. Hinuma, Y.; Nagata, K.; Hanaoka, M.; Nakai, M.; Matsumoto, T.; Kinoshita, K.I.; Shirakawa, S.; Miyoshi, I. Adult T-cell leukemia: Antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc. Natl. Acad. Sci. USA 1981, 78, 6476–6480. [Google Scholar] [CrossRef] [PubMed]
  168. Poiesz, B.J.; Ruscetti, F.W.; Gazdar, A.F.; Bunn, P.A.; Minna, J.D.; Gallo, R.C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. USA 1980, 77, 7415–7419. [Google Scholar] [CrossRef] [PubMed]
  169. Yoshida, M.; Miyoshi, I.; Hinuma, Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc. Natl. Acad. Sci. USA 1982, 79, 2031–2035. [Google Scholar] [CrossRef] [PubMed]
  170. Watanabe, T.; Seiki, M.; Yoshida, M. HTLV type I (U. S. Isolate) and ATLV (Japanese isolate) are the same species of human retrovirus. Virology 1984, 133, 238–241. [Google Scholar] [CrossRef] [PubMed]
  171. Kwok, S.; Kellogg, D.; Ehrlich, G.; Poiesz, B.; Bhagavati, S.; Sninsky, J.J. Characterization of a sequence of human T cell leukemia virus type I from a patient with chronic progressive myelopathy. J. Infect. Dis. 1988, 158, 1193–1197. [Google Scholar] [CrossRef] [PubMed]
  172. Mochizuki, M.; Tajima, K.; Watanabe, T.; Yamaguchi, K. Human T lymphotropic virus type 1 uveitis. Br. J. Ophthalmol. 1994, 78, 149–154. [Google Scholar] [CrossRef] [PubMed]
  173. Satake, M.; Yamaguchi, K.; Tadokoro, K. Current prevalence of HTLV-1 in Japan as determined by screening of blood donors. J. Med. Virol. 2012, 84, 327–335. [Google Scholar] [CrossRef] [PubMed]
  174. Kishihara, Y.; Furusyo, N.; Kashiwagi, K.; Mitsutake, A.; Kashiwagi, S.; Hayashi, J. Human T lymphotropic virus type 1 infection influences hepatitis C virus clearance. J. Infect. Dis. 2001, 184, 1114–1119. [Google Scholar] [CrossRef] [PubMed]
  175. Proietti, F.A.; Carneiro-Proietti, A.B.; Catalan-Soares, B.C.; Murphy, E.L. Global epidemiology of HTLV-I infection and associated diseases. Oncogene 2005, 24, 6058–6068. [Google Scholar] [CrossRef] [PubMed]
  176. Hlela, C.; Shepperd, S.; Khumalo, N.P.; Taylor, G.P. The prevalence of human T-cell lymphotropic virus type 1 in the general population is unknown. AIDS Rev. 2009, 11, 205–214. [Google Scholar] [PubMed]
  177. Li, H.C.; Biggar, R.J.; Miley, W.J.; Maloney, E.M.; Cranston, B.; Hanchard, B.; Hisada, M. Provirus load in breast milk and risk of mother-to-child transmission of human T lymphotropic virus type I. J. Infect. Dis. 2004, 190, 1275–1278. [Google Scholar] [CrossRef] [PubMed]
  178. Mueller, N.; Okayama, A.; Stuver, S.; Tachibana, N. Findings from the Miyazaki cohort study. J. Acquir. Immune Defic. Syndr. Hum. Retrovirology : Off. Publ. Int. Retrovirology Assoc. 1996, 13 Suppl 1, S2–S7. [Google Scholar] [CrossRef]
  179. Stuver, S.O.; Tachibana, N.; Okayama, A.; Shioiri, S.; Tsunetoshi, Y.; Tsuda, K.; Mueller, N.E. Heterosexual transmission of human T cell leukemia/lymphoma virus type I among married couples in southwestern Japan: An initial report from the Miyazaki cohort study. J. Infect. Dis. 1993, 167, 57–65. [Google Scholar] [CrossRef] [PubMed]
  180. Manns, A.; Murphy, E.L.; Wilks, R.; Haynes, G.; Figueroa, J.P.; Hanchard, B.; Barnett, M.; Drummond, J.; Waters, D.; Cerney, M.; et al. Detection of early human T-cell lymphotropic virus type I antibody patterns during seroconversion among transfusion recipients. Blood 1991, 77, 896–905. [Google Scholar] [PubMed]
  181. Jones, K.S.; Petrow-Sadowski, C.; Huang, Y.K.; Bertolette, D.C.; Ruscetti, F.W. Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells. Nat. Med. 2008, 14, 429–436. [Google Scholar] [CrossRef] [PubMed]
  182. Hanon, E.; Stinchcombe, J.C.; Saito, M.; Asquith, B.E.; Taylor, G.P.; Tanaka, Y.; Weber, J.N.; Griffiths, G.M.; Bangham, C.R. Fratricide among CD8(+) T lymphocytes naturally infected with human T cell lymphotropic virus type I. Immunity 2000, 13, 657–664. [Google Scholar] [CrossRef] [PubMed]
  183. Hoxie, J.A.; Matthews, D.M.; Cines, D.B. Infection of human endothelial cells by human T-cell leukemia virus type I. Proc. Natl. Acad. Sci. USA 1984, 81, 7591–7595. [Google Scholar] [CrossRef] [PubMed]
  184. Derse, D.; Hill, S.A.; Lloyd, P.A.; Chung, H.; Morse, B.A. Examining human T-lymphotropic virus type 1 infection and replication by cell-free infection with recombinant virus vectors. J. Virol. 2001, 75, 8461–8468. [Google Scholar] [CrossRef] [PubMed]
  185. Lambert, S.; Bouttier, M.; Vassy, R.; Seigneuret, M.; Petrow-Sadowski, C.; Janvier, S.; Heveker, N.; Ruscetti, F.W.; Perret, G.; Jones, K.S.; et al. HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165. Blood 2009, 113, 5176–5185. [Google Scholar] [CrossRef] [PubMed]
  186. Pique, C.; Jones, K.S. Pathways of cell-cell transmission of HTLV-1. Front. Microbiol. 2012, 3, e378. [Google Scholar] [CrossRef]
  187. Pique, C.; Pham, D.; Tursz, T.; Dokhelar, M.C. Human T-cell leukemia virus type I envelope protein maturation process: Requirements for syncytium formation. J. Virol. 1992, 66, 906–913. [Google Scholar] [PubMed]
  188. Jones, K.S.; Lambert, S.; Bouttier, M.; Benit, L.; Ruscetti, F.W.; Hermine, O.; Pique, C. Molecular aspects of HTLV-1 entry: Functional domains of the HTLV-1 surface subunit (SU) and their relationships to the entry receptors. Viruses 2011, 3, 794–810. [Google Scholar] [CrossRef] [PubMed]
  189. Pinon, J.D.; Klasse, P.J.; Jassal, S.R.; Welson, S.; Weber, J.; Brighty, D.W.; Sattentau, Q.J. Human T-cell leukemia virus type 1 envelope glycoprotein gp46 interacts with cell surface heparan sulfate proteoglycans. J. Virol. 2003, 77, 9922–9930. [Google Scholar] [CrossRef] [PubMed]
  190. Jones, K.S.; Fugo, K.; Petrow-Sadowski, C.; Huang, Y.; Bertolette, D.C.; Lisinski, I.; Cushman, S.W.; Jacobson, S.; Ruscetti, F.W. Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 use different receptor complexes to enter T cells. J. Virol. 2006, 80, 8291–8302. [Google Scholar] [CrossRef] [PubMed]
  191. Jones, K.S.; Petrow-Sadowski, C.; Bertolette, D.C.; Huang, Y.; Ruscetti, F.W. Heparan sulfate proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells. J. Virol. 2005, 79, 12692–12702. [Google Scholar] [CrossRef] [PubMed]
  192. Tanaka, A.; Jinno-Oue, A.; Shimizu, N.; Hoque, A.; Mori, T.; Islam, S.; Nakatani, Y.; Shinagawa, M.; Hoshino, H. Entry of human T-cell leukemia virus type 1 is augmented by heparin sulfate proteoglycans bearing short heparin-like structures. J. Virol. 2012, 86, 2959–2969. [Google Scholar] [CrossRef] [PubMed]
  193. Ghez, D.; Lepelletier, Y.; Lambert, S.; Fourneau, J.M.; Blot, V.; Janvier, S.; Arnulf, B.; van Endert, P.M.; Heveker, N.; Pique, C.; et al. Neuropilin-1 is involved in human T-cell lymphotropic virus type 1 entry. J. Virol. 2006, 80, 6844–6854. [Google Scholar] [CrossRef] [PubMed]
  194. Soker, S.; Takashima, S.; Miao, H.Q.; Neufeld, G.; Klagsbrun, M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998, 92, 735–745. [Google Scholar] [CrossRef] [PubMed]
  195. Vander Kooi, C.W.; Jusino, M.A.; Perman, B.; Neau, D.B.; Bellamy, H.D.; Leahy, D.J. Structural basis for ligand and heparin binding to neuropilin B domains. Proc. Natl. Acad. Sci. USA 2007, 104, 6152–6157. [Google Scholar] [CrossRef] [PubMed]
  196. Jin, Q.; Agrawal, L.; VanHorn-Ali, Z.; Alkhatib, G. Infection of CD4+ T lymphocytes by the human T cell leukemia virus type 1 is mediated by the glucose transporter GLUT-1: Evidence using antibodies specific to the receptor's large extracellular domain. Virology 2006, 349, 184–196. [Google Scholar] [CrossRef] [PubMed]
  197. Manel, N.; Kim, F.J.; Kinet, S.; Taylor, N.; Sitbon, M.; Battini, J.L. The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Cell 2003, 115, 449–459. [Google Scholar] [CrossRef] [PubMed]
  198. Igakura, T.; Stinchcombe, J.C.; Goon, P.K.; Taylor, G.P.; Weber, J.N.; Griffiths, G.M.; Tanaka, Y.; Osame, M.; Bangham, C.R. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 2003, 299, 1713–1716. [Google Scholar] [CrossRef] [PubMed]
  199. Barnard, A.L.; Igakura, T.; Tanaka, Y.; Taylor, G.P.; Bangham, C.R. Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes. Blood 2005, 106, 988–995. [Google Scholar] [CrossRef] [PubMed]
  200. Hildreth, J.E.; Subramanium, A.; Hampton, R.A. Human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation mediated by vascular cell adhesion molecule-1: Evidence for involvement of cell adhesion molecules in HTLV-1 biology. J. Virol. 1997, 71, 1173–1180. [Google Scholar] [PubMed]
  201. Daenke, S.; McCracken, S.A.; Booth, S. Human T-cell leukaemia/lymphoma virus type 1 syncytium formation is regulated in a cell-specific manner by ICAM-1, ICAM-3 and VCAM-1 and can be inhibited by antibodies to integrin beta2 or beta7. J. Gen. Virol. 1999, 80, 1429–1436. [Google Scholar] [PubMed]
  202. Takenouchi, N.; Jones, K.S.; Lisinski, I.; Fugo, K.; Yao, K.; Cushman, S.W.; Ruscetti, F.W.; Jacobson, S. GLUT1 is not the primary binding receptor but is associated with cell-to-cell transmission of human T-cell leukemia virus type 1. J. Virol. 2007, 81, 1506–1510. [Google Scholar] [CrossRef] [PubMed]
  203. Nejmeddine, M.; Barnard, A.L.; Tanaka, Y.; Taylor, G.P.; Bangham, C.R. Human T-lymphotropic virus, type 1, tax protein triggers microtubule reorientation in the virological synapse. J. Biol. Chem. 2005, 280, 29653–29660. [Google Scholar] [CrossRef] [PubMed]

Share and Cite

MDPI and ACS Style

Schäfer, G.; Blumenthal, M.J.; Katz, A.A. Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry. Viruses 2015, 7, 2592-2617. https://doi.org/10.3390/v7052592

AMA Style

Schäfer G, Blumenthal MJ, Katz AA. Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry. Viruses. 2015; 7(5):2592-2617. https://doi.org/10.3390/v7052592

Chicago/Turabian Style

Schäfer, Georgia, Melissa J. Blumenthal, and Arieh A. Katz. 2015. "Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry" Viruses 7, no. 5: 2592-2617. https://doi.org/10.3390/v7052592

Article Metrics

Back to TopTop