E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Kaposi's Sarcoma-Associated Herpesvirus"

Quicklinks

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 October 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Zhi-Ming Zheng (Website)

Head, Tumor Virus RNA Biology Section, Senior Investigator, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Fax: +301 480 8250

Special Issue Information

Dear Colleagues,

The discovery of KSHV in 1994 has been a historical landmark in tumor virology and human cancer research. This remarkable finding soon attracted hundreds of research laboratories and thousands of virologists and oncologists to switch their research directions. To date, PubMed has collected more than 4710 papers on KSHV from numerous journal publications in the world. These studies reiterate the global fight against human cancers which will continue to receive great support from our tremendous efforts in searching for new tumor-causing viruses and in understanding the basic biology of tumor viruses. To celebrate the 20th years of KSHV discovery, we are very proud to publish a special issue on KSHV in 2014 in Viruses. This special issue will explore all aspects of KSHV, including updated reviews and research articles. We are looking forward to your contribution and to publishing your important discoveries in this special issue.

Zhi-Ming Zheng 
Guest Editor

KSV

17th International Workshop on Kaposi's Sarcoma Herpesvirus (KSHV) and Related Agents" 25 -28 July, 2014, Beijing, China, organized by Dr Hongyu Deng and Dr Ke Lan. Photograph by Prof Dirk Dittmer under the Creative Commons Attribution License 4.0

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs).

Print Edition available!
A Print Edition of this Special Issue is available here.

Name Pice* Download or order
Kaposi's Sarcoma-Associated Herpesvirus 50.50 CHF here
For contributing authors or bulk orders special prices may apply.
Prices include shipping.

Keywords

  • Virus epidemiology and transmission
  • virus entry
  • gene structure and expression
  • viral DNA replication
  • virus assembly and release
  • virus pathogenesis and oncogenesis
  • anti-KSHV therapy and prevention

 

Published Papers (16 papers)

View options order results:
result details:
Displaying articles 1-16
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity
Viruses 2015, 7(4), 1627-1641; doi:10.3390/v7041627
Received: 24 October 2014 / Revised: 6 January 2015 / Accepted: 20 March 2015 / Published: 31 March 2015
Cited by 2 | PDF Full-text (3341 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi’s Sarcoma (KS). KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi’s Sarcoma (KS). KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessCommunication Multiple Regions of Kaposi’s Sarcoma-Associated Herpesvirus ORF59 RNA are Required for Its Expression Mediated by Viral ORF57 and Cellular RBM15
Viruses 2015, 7(2), 496-510; doi:10.3390/v7020496
Received: 19 December 2014 / Revised: 15 January 2015 / Accepted: 28 January 2015 / Published: 3 February 2015
Cited by 4 | PDF Full-text (1129 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
KSHV ORF57 (MTA) promotes RNA stability of ORF59, a viral DNA polymerase processivity factor. Here, we show that the integrity of both ORF59 RNA ends is necessary for ORF57-mediated ORF59 expression and deletion of both 5’ and 3’ regions, or one end [...] Read more.
KSHV ORF57 (MTA) promotes RNA stability of ORF59, a viral DNA polymerase processivity factor. Here, we show that the integrity of both ORF59 RNA ends is necessary for ORF57-mediated ORF59 expression and deletion of both 5’ and 3’ regions, or one end region with a central region, of ORF59 RNA prevents ORF57-mediated translation of ORF59. The ORF59 sequence between nt 96633 and 96559 resembles other known MTA-responsive elements (MREs). ORF57 specifically binds to a stem-loop region from nt 96596–96572 of the MRE, which also binds cellular RBM15. Internal deletion of the MRE from ORF59 led to poor export, but accumulation of nuclear ORF59 RNA in the presence of ORF57 or RBM15. Despite of being translatable in the presence of ORF57, this deletion mutant exhibits translational defect in the presence of RBM15. Together, our results provide novel insight into the roles of ORF57 and RBM15 in ORF59 RNA accumulation and protein translation. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessArticle Genotypic Analysis of Kaposi’s Sarcoma-Associated Herpesvirus from Patients with Kaposi’s Sarcoma in Xinjiang, China
Viruses 2014, 6(12), 4800-4810; doi:10.3390/v6124800
Received: 27 September 2014 / Revised: 9 November 2014 / Accepted: 17 November 2014 / Published: 26 November 2014
PDF Full-text (569 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causal agent of all forms of Kaposi’s sarcoma (KS), including AIDS-KS, endemic KS, classic KS and iatrogenic KS. Based on Open reading frame (ORF) K1 sequence analysis, KSHV has been classified into seven major molecular subtypes [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causal agent of all forms of Kaposi’s sarcoma (KS), including AIDS-KS, endemic KS, classic KS and iatrogenic KS. Based on Open reading frame (ORF) K1 sequence analysis, KSHV has been classified into seven major molecular subtypes (A, B, C, D, E, F and Z). The distribution of KSHV strains varies according to geography and ethnicity. Xinjiang is a unique region where the seroprevalence of KSHV is significantly higher than other parts of China. The genotyping of KSHV strains in this region has not been thoroughly studied. The present study aimed to evaluate the frequency of KSHV genotypes isolated from KS tissues in Classical KS and AIDS KS patients from Xinjiang, China. ORF-K1 of KSHV from tissue samples of 28 KS patients was amplified and sequenced. Two subtypes of KSHV were identified according to K1 genotyping. Twenty-three of them belonged to subtype A, while five of them were subtype C. More genotype A than genotype C strains were found in both Classical KS and AIDS KS. No significant difference was found in the prevalence of different genotype between Classical KS and AIDS KS. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessArticle KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors
Viruses 2014, 6(10), 4005-4023; doi:10.3390/v6104005
Received: 9 September 2014 / Revised: 17 October 2014 / Accepted: 21 October 2014 / Published: 23 October 2014
Cited by 11 | PDF Full-text (905 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 deletion mutant viruses displayed increased spontaneous reactivation and were more sensitive to inducers of reactivation than cells infected with wild type KSHV. Predicted binding sites for miR-K12-3 and miR-K12-11 were found in the 3’UTRs of the cellular transcription factors MYB, Ets-1, and C/EBPα, which activate RTA, the KSHV replication and transcription activator. Targeting of MYB by miR-K12-11 was confirmed by cloning the MYB 3’UTR downstream from the luciferase reporter. Knockdown of miR‑K12-11 resulted in increased levels of MYB transcript, and knockdown of miR-K12-3 increased both C/EBPα and Ets-1 transcripts. Thus, miR-K12-11 and miR-K12-3 contribute to maintenance of latency by decreasing RTA expression indirectly, presumably via down‑regulation of MYB, C/EBPα and Ets-1, and possibly other host transcription factors. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessArticle Seroprevalence of Human Herpesvirus 8 and Hepatitis C Virus among Drug Users in Shanghai, China
Viruses 2014, 6(6), 2519-2530; doi:10.3390/v6062519
Received: 1 April 2014 / Revised: 2 June 2014 / Accepted: 6 June 2014 / Published: 23 June 2014
Cited by 1 | PDF Full-text (610 KB) | HTML Full-text | XML Full-text
Abstract
To elucidate and compare the seroprevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) among Chinese drug users, a cross-sectional study of 441 participants, was conducted in Shanghai, China, from 2012 through 2013. Seventy-seven (17.5%) participants were found to be [...] Read more.
To elucidate and compare the seroprevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) among Chinese drug users, a cross-sectional study of 441 participants, was conducted in Shanghai, China, from 2012 through 2013. Seventy-seven (17.5%) participants were found to be positive for HHV8 antibodies, while 271 (61.5%) participants were positive for HCV. No significant association between HHV8 seropositivity and drug use characteristics, sexual behaviors, HCV, or syphilis was observed. In contrast, a statistically significant association between HCV seropositivity and injected drug history (OR, 2.18, 95% CI 1.41–3.37) was detected, whereas no statistically significant association between HCV seropositivity and syphilis infection (OR, 7.56, 95% CI 0.94–60.57) were observed. Pairwise comparisons showed no significant differences between latent and lytic antibodies regarding HCV and HHV8 serostatus. The study demonstrated a moderate but elevated prevalence of HHV8 infection among drug users. The discordance between HHV8 and HCV infections suggests that blood borne transmission of HHV8 might not be the predominant mode of transmission in this population, which is in contrast to HCV. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available

Review

Jump to: Research, Other

Open AccessReview KSHV ORF57, a Protein of Many Faces
Viruses 2015, 7(2), 604-633; doi:10.3390/v7020604
Received: 29 November 2014 / Accepted: 2 February 2015 / Published: 10 February 2015
Cited by 5 | PDF Full-text (2013 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF57 protein (also known as mRNA transcript accumulation (Mta)) is a potent posttranscriptional regulator essential for the efficient expression of KSHV lytic genes and productive KSHV replication. ORF57 possesses numerous activities that promote the expression of viral genes, [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF57 protein (also known as mRNA transcript accumulation (Mta)) is a potent posttranscriptional regulator essential for the efficient expression of KSHV lytic genes and productive KSHV replication. ORF57 possesses numerous activities that promote the expression of viral genes, including the three major functions of enhancement of RNA stability, promotion of RNA splicing, and stimulation of protein translation. The multifunctional nature of ORF57 is driven by its ability to interact with an array of cellular cofactors. These interactions are required for the formation of ORF57-containing ribonucleoprotein complexes at specific binding sites in the target transcripts, referred as Mta-responsive elements (MREs). Understanding of the ORF57 protein conformation has led to the identification of two structurally-distinct domains within the ORF57 polypeptide: an unstructured intrinsically disordered N-terminal domain and a structured α-helix-rich C-terminal domain. The distinct structures of the domains serve as the foundation for their unique binding affinities: the N-terminal domain mediates ORF57 interactions with cellular cofactors and target RNAs, and the C-terminal domain mediates ORF57 homodimerization. In addition, each domain has been found to contribute to the stability of ORF57 protein in infected cells by counteracting caspase- and proteasome-mediated degradation pathways. Together, these new findings provide insight into the function and biological properties of ORF57 in the KSHV life cycle and pathogenesis. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Figures

Open AccessReview Molecular Biology of KSHV Lytic Reactivation
Viruses 2015, 7(1), 116-153; doi:10.3390/v7010116
Received: 31 October 2014 / Accepted: 5 January 2015 / Published: 14 January 2015
Cited by 6 | PDF Full-text (1442 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) primarily persists as a latent episome in infected cells. During latent infection, only a limited number of viral genes are expressed that help to maintain the viral episome and prevent lytic reactivation. The latent KSHV genome persists as [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) primarily persists as a latent episome in infected cells. During latent infection, only a limited number of viral genes are expressed that help to maintain the viral episome and prevent lytic reactivation. The latent KSHV genome persists as a highly ordered chromatin structure with bivalent chromatin marks at the promoter-regulatory region of the major immediate-early gene promoter. Various stimuli can induce chromatin modifications to an active euchromatic epigenetic mark, leading to the expression of genes required for the transition from the latent to the lytic phase of KSHV life cycle. Enhanced replication and transcription activator (RTA) gene expression triggers a cascade of events, resulting in the modulation of various cellular pathways to support viral DNA synthesis. RTA also binds to the origin of lytic DNA replication to recruit viral, as well as cellular, proteins for the initiation of the lytic DNA replication of KSHV. In this review we will discuss some of the pivotal genetic and epigenetic factors that control KSHV reactivation from the transcriptionally restricted latent program. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control
Viruses 2015, 7(1), 72-109; doi:10.3390/v7010072
Received: 18 September 2014 / Accepted: 30 December 2014 / Published: 12 January 2015
Cited by 4 | PDF Full-text (3006 KB) | HTML Full-text | XML Full-text
Abstract
In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, [...] Read more.
In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and the viral Mta protein. Given that robust viral reactivation would facilitate antiviral responses and culminate in host cell lysis, regulation of Rta’s expression and function is a major determinant of the latent-lytic balance and the fate of infected cells. Our lab recently showed that Rta transactivation requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest that proline‑directed phosphorylation regulates Rta by licensing binding to Pin1. Despite Pin1’s ability to stimulate Rta transactivation, unchecked Pin1 activity inhibited virus production. Dysregulation of Pin1 is implicated in human cancers, and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1 is a molecular timer that can regulate the balance between viral lytic gene expression and host cell lysis. Intriguing scenarios for Pin1’s underlying activities, and the potential broader significance for isomerization of Rta and reactivation, are highlighted. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview KSHV LANA—The Master Regulator of KSHV Latency
Viruses 2014, 6(12), 4961-4998; doi:10.3390/v6124961
Received: 30 October 2014 / Revised: 3 December 2014 / Accepted: 5 December 2014 / Published: 11 December 2014
Cited by 13 | PDF Full-text (991 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma associated herpesvirus (KSHV), like other human herpes viruses, establishes a biphasic life cycle referred to as dormant or latent, and productive or lytic phases. The latent phase is characterized by the persistence of viral episomes in a highly ordered chromatin [...] Read more.
Kaposi’s sarcoma associated herpesvirus (KSHV), like other human herpes viruses, establishes a biphasic life cycle referred to as dormant or latent, and productive or lytic phases. The latent phase is characterized by the persistence of viral episomes in a highly ordered chromatin structure and with the expression of a limited number of viral genes. Latency Associated Nuclear Antigen (LANA) is among the most abundantly expressed proteins during latency and is required for various nuclear functions including the recruitment of cellular machineries for viral DNA replication and segregation of the replicated genomes to daughter cells. LANA achieves these functions by recruiting cellular proteins including replication factors, chromatin modifying enzymes and cellular mitotic apparatus assembly. LANA directly binds to the terminal repeat region of the viral genome and associates with nucleosomal proteins to tether to the host chromosome. Binding of LANA to TR recruits the replication machinery, thereby initiating DNA replication within the TR. However, other regions of the viral genome can also initiate replication as determined by Single Molecule Analysis of the Replicated DNA (SMARD) approach. Recent, next generation sequence analysis of the viral transcriptome shows the expression of additional genes during latent phase. Here, we discuss the newly annotated latent genes and the role of major latent proteins in KSHV biology. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Figures

Open AccessReview KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication
Viruses 2014, 6(11), 4731-4759; doi:10.3390/v6114731
Received: 23 July 2014 / Revised: 7 November 2014 / Accepted: 17 November 2014 / Published: 24 November 2014
Cited by 3 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. Since the discovery of KSHV 20 years ago, there is still no standard treatment and the management of virus-associated malignancies remains toxic and incompletely [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. Since the discovery of KSHV 20 years ago, there is still no standard treatment and the management of virus-associated malignancies remains toxic and incompletely efficacious. As the majority of tumor cells are latently infected with KSHV, currently marketed antivirals that target the virus lytic cycle have shown inconsistent results in clinic. Nevertheless, lytic replication plays a major role in disease progression and virus dissemination. Case reports and retrospective studies have pointed out the benefit of antiviral therapy in the treatment and prevention of KSHV-associated diseases. As a consequence, potent and selective antivirals are needed. This review focuses on the anti-KSHV activity, mode of action and current status of antiviral drugs targeting KSHV lytic cycle. Among these drugs, different subclasses of viral DNA polymerase inhibitors and compounds that do not target the viral DNA polymerase are being discussed. We also cover molecules that target cellular kinases, as well as the potential of new drug targets and animal models for antiviral testing. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview Long Non-Coding RNA and Epigenetic Gene Regulation of KSHV
Viruses 2014, 6(11), 4165-4177; doi:10.3390/v6114165
Received: 1 August 2014 / Revised: 21 October 2014 / Accepted: 22 October 2014 / Published: 4 November 2014
Cited by 6 | PDF Full-text (574 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV/human herpesvirus 8) is a γ-herpesvirus linked to Kaposi’s sarcoma (KS) and two lymphoproliferative disorders, primary effusion lymphoma (PEL or body-cavity B-lymphoma [BCBL]) and a subset of Multicentric Castleman’s Disease. During lytic growth, pervasive viral transcription generating a variety [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV/human herpesvirus 8) is a γ-herpesvirus linked to Kaposi’s sarcoma (KS) and two lymphoproliferative disorders, primary effusion lymphoma (PEL or body-cavity B-lymphoma [BCBL]) and a subset of Multicentric Castleman’s Disease. During lytic growth, pervasive viral transcription generating a variety of transcripts with uncertain protein-coding potential has been described on a genome-wide scale in β- and γ-herpesviruses. One class of such RNAs is called long non-coding RNAs (lncRNAs). KSHV encodes a viral lncRNA known as polyadenylated nuclear RNA (PAN RNA), a copious early gene product. PAN RNA has been implicated in KSHV gene expression, replication, and immune modulation. PAN RNA expression is required for optimal expression of the entire KSHV lytic gene expression program. Latent KSHV episomes are coated with viral latency-associated nuclear antigen (LANA). LANA rapidly dissociates from episomes during reactivation. Here we review recent studies suggesting that PAN RNA may function as a viral lncRNA, including a role in the facilitation of LANA-episomal dissociation during lytic replication. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview Epidemiology and Transmission of Kaposi’s Sarcoma-Associated Herpesvirus
Viruses 2014, 6(11), 4178-4194; doi:10.3390/v6114178
Received: 2 September 2014 / Revised: 14 October 2014 / Accepted: 23 October 2014 / Published: 4 November 2014
Cited by 4 | PDF Full-text (653 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes the current knowledge pertaining to Kaposi sarcoma-associated herpesvirus (KSHV) epidemiology and transmission. Since the identification of KSHV twenty years ago, it is now known to be associated with Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease. Many [...] Read more.
This review summarizes the current knowledge pertaining to Kaposi sarcoma-associated herpesvirus (KSHV) epidemiology and transmission. Since the identification of KSHV twenty years ago, it is now known to be associated with Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease. Many studies have been conducted to understand its epidemiology and pathogenesis and their results clearly show that the worldwide distribution of KSHV is uneven. Some geographical areas, such as sub-Saharan Africa, the Mediterranean region and the Xinjiang region of China, are endemic areas, but Western Europe and United States have a low prevalence in the general population. This makes it imperative to understand the risk factors associated with acquisition of infection. KSHV can be transmitted via sexual contact and non-sexual routes, such as transfusion of contaminated blood and tissues transplants, or via saliva contact. There is now a general consensus that salivary transmission is the main route of transmission, especially in children residing in endemic areas. Therefore, there is a need to better understand the sources of transmission to young children. Additionally, lack of animal models to study transmission, gold standard serological assay and the lack of emphasis on endemic KS research has hampered the efforts to further delineate KSHV transmission in order to design effective prevention strategies. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview PAN’s Labyrinth: Molecular Biology of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) PAN RNA, a Multifunctional Long Noncoding RNA
Viruses 2014, 6(11), 4212-4226; doi:10.3390/v6114212
Received: 9 September 2014 / Revised: 23 October 2014 / Accepted: 24 October 2014 / Published: 4 November 2014
Cited by 9 | PDF Full-text (611 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesivrus, the causative agent of Kaposi’s sarcoma and body cavity lymphomas. During infection KSHV produces a highly abundant long non-coding polyadenylated RNA that is retained in the nucleus known as PAN RNA. Long noncoding RNAs [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesivrus, the causative agent of Kaposi’s sarcoma and body cavity lymphomas. During infection KSHV produces a highly abundant long non-coding polyadenylated RNA that is retained in the nucleus known as PAN RNA. Long noncoding RNAs (lncRNA) are key regulators of gene expression and are known to interact with specific chromatin modification complexes, working in cis and trans to regulate gene expression. Data strongly supports a model where PAN RNA is a multifunctional regulatory transcript that controls KSHV gene expression by mediating the modification of chromatin by targeting the KSHV repressed genome. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview Interaction of KSHV with Host Cell Surface Receptors and Cell Entry
Viruses 2014, 6(10), 4024-4046; doi:10.3390/v6104024
Received: 17 August 2014 / Revised: 19 October 2014 / Accepted: 21 October 2014 / Published: 23 October 2014
Cited by 8 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text
Abstract
Virus entry is a complex process characterized by a sequence of events. Since the discovery of KSHV in 1994, tremendous progress has been made in our understanding of KSHV entry into its in vitro target cells. KSHV entry is a complex multistep [...] Read more.
Virus entry is a complex process characterized by a sequence of events. Since the discovery of KSHV in 1994, tremendous progress has been made in our understanding of KSHV entry into its in vitro target cells. KSHV entry is a complex multistep process involving viral envelope glycoproteins and several cell surface molecules that is utilized by KSHV for its attachment and entry. KSHV has a broad cell tropism and the attachment and receptor engagement on target cells have an important role in determining the cell type-specific mode of entry. KSHV utilizes heparan sulfate, integrins and EphrinA2 molecules as receptors which results in the activation of host cell pre-existing signal pathways that facilitate the subsequent cascade of events resulting in the rapid entry of virus particles, trafficking towards the nucleus followed by viral and host gene expression. KSHV enters human fibroblast cells by dynamin dependant clathrin mediated endocytosis and by dynamin independent macropinocytosis in dermal endothelial cells. Once internalized into endosomes, fusion of the viral envelope with the endosomal membranes in an acidification dependent manner results in the release of capsids which subsequently reaches the nuclear pore vicinity leading to the delivery of viral DNA into the nucleus. In this review, we discuss the principal mechanisms that enable KSHV to interact with the host cell surface receptors as well as the mechanisms that are required to modulate cell signaling machinery for a successful entry. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available
Open AccessReview Contribution of Viral Mimics of Cellular Genes to KSHV Infection and Disease
Viruses 2014, 6(9), 3472-3486; doi:10.3390/v6093472
Received: 11 August 2014 / Revised: 5 September 2014 / Accepted: 11 September 2014 / Published: 19 September 2014
Cited by 1 | PDF Full-text (406 KB) | HTML Full-text | XML Full-text
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8) is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV is a double-stranded DNA virus that encodes [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8) is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6) is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available

Other

Jump to: Research, Review

Open AccessEssay Twenty Years of KSHV
Viruses 2014, 6(11), 4258-4264; doi:10.3390/v6114258
Received: 6 October 2014 / Revised: 29 October 2014 / Accepted: 30 October 2014 / Published: 7 November 2014
Cited by 3 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text
Abstract
Twenty years ago, Kaposi’s sarcoma (KS) was the oncologic counterpart to Winston Churchill’s Russia: a riddle, wrapped in a mystery, inside an enigma. First described by Moritz Kaposi in 1872, who reported it to be an aggressive skin tumor, KS became known [...] Read more.
Twenty years ago, Kaposi’s sarcoma (KS) was the oncologic counterpart to Winston Churchill’s Russia: a riddle, wrapped in a mystery, inside an enigma. First described by Moritz Kaposi in 1872, who reported it to be an aggressive skin tumor, KS became known over the next century as a slow-growing tumor of elderly men—in fact, most KS patients were expected to die with the tumor rather than from it. Nevertheless, the course and manifestations of the disease varied widely in different clinical contexts. The puzzle of KS came to the forefront as a harbinger of the AIDS epidemic. The articles in this issue of Viruses recount progress made in understanding Kaposi’s sarcoma herpesvirus (KSHV) since its initial description in 1994. Full article
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus) Print Edition available

Journal Contact

MDPI AG
Viruses Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
viruses@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Viruses
Back to Top