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Viruses, Volume 4, Issue 9 (September 2012), Pages 1372-1843

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Research

Jump to: Review

Open AccessArticle Renal Alterations in Feline Immunodeficiency Virus (FIV)-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes
Viruses 2012, 4(9), 1372-1389; doi:10.3390/v4091372
Received: 18 July 2012 / Revised: 15 August 2012 / Accepted: 16 August 2012 / Published: 27 August 2012
Cited by 10 | PDF Full-text (3747 KB) | HTML Full-text | XML Full-text
Abstract
Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the
[...] Read more.
Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. Full article
(This article belongs to the Special Issue Feline Retroviruses)
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Open AccessArticle Genetics-Based Classification of Filoviruses Calls for Expanded Sampling of Genomic Sequences
Viruses 2012, 4(9), 1425-1437; doi:10.3390/v4091425
Received: 3 July 2012 / Revised: 23 August 2012 / Accepted: 24 August 2012 / Published: 31 August 2012
Cited by 11 | PDF Full-text (1174 KB) | HTML Full-text | XML Full-text
Abstract
We have recently developed a computational approach for hierarchical, genome-based classification of viruses of a family (DEmARC). In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of
[...] Read more.
We have recently developed a computational approach for hierarchical, genome-based classification of viruses of a family (DEmARC). In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of the classification. Here, we apply DEmARC to a set of 56 filoviruses with complete genome sequences and compare the resulting classification to the ICTV taxonomy of the family Filoviridae. We find in total six candidate taxon levels two of which correspond to the species and genus ranks of the family. At these two levels, the six filovirus species and two genera officially recognized by ICTV, as well as a seventh tentative species for Lloviu virus and prototyping a third genus, are reproduced. DEmARC lends the highest possible support for these two as well as the four other levels, implying that the actual number of valid taxon levels remains uncertain and the choice of levels for filovirus species and genera is arbitrary. Based on our experience with other virus families, we conclude that the current sampling of filovirus genomic sequences needs to be considerably expanded in order to resolve these uncertainties in the framework of genetics-based classification. Full article
(This article belongs to the Special Issue Advances in Filovirus Research 2012) Print Edition available
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Open AccessArticle Genomic Sequences of Two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombination in Environmental Strains
Viruses 2012, 4(9), 1548-1568; doi:10.3390/v4091548
Received: 19 July 2012 / Revised: 30 August 2012 / Accepted: 3 September 2012 / Published: 13 September 2012
Cited by 1 | PDF Full-text (934 KB) | HTML Full-text | XML Full-text
Abstract
Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal waters 1130 km apart (North
[...] Read more.
Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal waters 1130 km apart (North Carolina and Rhode Island, USA), these strains shared 97% nucleotide similarity and 97–100% amino acid similarity. When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. Further bioinformatic analyses suggested a recombination event occurred. To the best of our knowledge, this is the first description of viral recombinants in environmental Leviviridae ssRNA bacteriophages. Full article
(This article belongs to the Special Issue Recent Progress in Bacteriophage Research) Print Edition available
Open AccessArticle Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa
Viruses 2012, 4(9), 1592-1604; doi:10.3390/v4091592
Received: 13 August 2012 / Revised: 30 August 2012 / Accepted: 30 August 2012 / Published: 13 September 2012
Cited by 3 | PDF Full-text (662 KB) | HTML Full-text | XML Full-text
Abstract
Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. Since the reemergence of Ebola virus
[...] Read more.
Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. Since the reemergence of Ebola virus in Central Africa, the CIRMF “Emerging Viral Disease Unit” developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. The Unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and Ebola virus pathogenesis. In addition, academic training is provided at all levels to regional and international students covering emerging conditions (host factors, molecular biology, genetics) that favor the spread of viral diseases. Full article
(This article belongs to the Special Issue Advances in Filovirus Research 2012) Print Edition available
Open AccessArticle Cytopathogenesis of Vesicular Stomatitis Virus Is Regulated by the PSAP Motif of M Protein in a Species-Dependent Manner
Viruses 2012, 4(9), 1605-1618; doi:10.3390/v4091605
Received: 10 August 2012 / Revised: 11 September 2012 / Accepted: 12 September 2012 / Published: 19 September 2012
Cited by 4 | PDF Full-text (1872 KB) | HTML Full-text | XML Full-text
Abstract
Vesicular stomatitis virus (VSV) is an important vector-borne pathogen of bovine and equine species, causing a reportable vesicular disease. The matrix (M) protein of VSV is multifunctional and plays a key role in cytopathogenesis, apoptosis, host protein shut-off, and virion assembly/budding. Our previous
[...] Read more.
Vesicular stomatitis virus (VSV) is an important vector-borne pathogen of bovine and equine species, causing a reportable vesicular disease. The matrix (M) protein of VSV is multifunctional and plays a key role in cytopathogenesis, apoptosis, host protein shut-off, and virion assembly/budding. Our previous findings indicated that mutations of residues flanking the 37PSAP40 motif within the M protein resulted in VSV recombinants having attenuated phenotypes in mice. In this report, we characterize the phenotype of VSV recombinant PS > A4 (which harbors four alanines (AAAA) in place of the PSAP motif without disruption of flanking residues) in both mice, and in Aedes albopictus C6/36 mosquito and Culicoides sonorensis KC cell lines. The PS > A4 recombinant displayed an attenuated phenotype in infected mice as judged by weight loss, mortality, and viral titers measured from lung and brain samples of infected animals. However, unexpectedly, the PS > A4 recombinant displayed a robust cytopathic phenotype in insect C6/36 cells compared to that observed with control viruses. Notably, titers of recombinant PS > A4 were approximately 10-fold greater than those of control viruses in infected C6/36 cells and in KC cells from Culicoides sonorensis, a known VSV vector species. In addition, recombinant PS > A4 induced a 25-fold increase in the level of C3 caspase activity in infected C6/36 cells. These findings indicate that the PSAP motif plays a direct role in regulating cytopathogenicity in a species-dependent manner, and suggest that the intact PSAP motif may be important for maintaining persistence of VSV in an insect host. Full article
(This article belongs to the Special Issue Recent Findings on the Biology of Rhabdovirus)
Open AccessArticle PepGMV Rep-Protein Expression in Mammalian Cells
Viruses 2012, 4(9), 1792-1801; doi:10.3390/v4091792
Received: 27 July 2012 / Revised: 6 September 2012 / Accepted: 6 September 2012 / Published: 24 September 2012
PDF Full-text (613 KB) | HTML Full-text | XML Full-text
Abstract
The Geminiviruses genome is a small, single strand DNA that replicates in the plant cell nucleus. Analogous to animal DNA viruses, Geminiviruses depend on the host replication machinery to amplify their genomes and only supply the factors required to initiate their replication. Consequently, Geminiviruses
[...] Read more.
The Geminiviruses genome is a small, single strand DNA that replicates in the plant cell nucleus. Analogous to animal DNA viruses, Geminiviruses depend on the host replication machinery to amplify their genomes and only supply the factors required to initiate their replication. Consequently, Geminiviruses remove the cell-cycle arrest and induce the host replication machinery using an endocycle process. They encode proteins, such as the conserved replication-associated proteins (Rep) that interact with retinoblastoma-like proteins in plants and alter the cell division cycle in yeasts. Therefore, the aim of this work is to analyze the impact of Pepper Golden Mosaic Virus (PepGMV) Rep protein in mammalian cells. Results indicate that the pTracer-SV40:Rep construction obtained in this work can be used to analyze the Rep protein effect in mammalian cells in order to compare the cell cycle regulation mechanisms in plants and animals. Full article
(This article belongs to the Special Issue Plant Viruses)
Open AccessArticle Animal Models, Prophylaxis, and Therapeutics for Arenavirus Infections
Viruses 2012, 4(9), 1802-1829; doi:10.3390/v4091802
Received: 3 August 2012 / Revised: 19 September 2012 / Accepted: 21 September 2012 / Published: 24 September 2012
Cited by 7 | PDF Full-text (401 KB) | HTML Full-text | XML Full-text
Abstract
Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic
[...] Read more.
Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection. Full article
(This article belongs to the Special Issue Arenaviruses)
Open AccessArticle Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa
Viruses 2012, 4(9), 1830-1843; doi:10.3390/v4091830
Received: 26 July 2012 / Revised: 13 September 2012 / Accepted: 13 September 2012 / Published: 24 September 2012
PDF Full-text (595 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected
[...] Read more.
The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317. Full article
(This article belongs to the Special Issue HIV Dynamics and Evolution)

Review

Jump to: Research

Open AccessReview MicroRNA-Mediated Restriction of HIV-1 in Resting CD4+ T Cells and Monocytes
Viruses 2012, 4(9), 1390-1409; doi:10.3390/v4091390
Received: 18 June 2012 / Revised: 28 July 2012 / Accepted: 30 July 2012 / Published: 29 August 2012
Cited by 23 | PDF Full-text (2176 KB) | HTML Full-text | XML Full-text
Abstract
In contrast to activated CD4+ T cells and differentiated macrophages, resting CD4+ T cells and monocytes are non-permissive for HIV-1 replication. The mediators which regulate the resting or quiescent phenotype are often actively involved in the restriction of viral replication and
[...] Read more.
In contrast to activated CD4+ T cells and differentiated macrophages, resting CD4+ T cells and monocytes are non-permissive for HIV-1 replication. The mediators which regulate the resting or quiescent phenotype are often actively involved in the restriction of viral replication and the establishment and maintenance of viral latency. Recently, certain microRNAs which are highly expressed in resting cells have been implicated in this capacity, inhibiting the expression of cellular proteins that are also viral co-factors; following activation these microRNAs exhibit decreased expression, while their targets are correspondingly up-regulated, contributing to a favorable milieu for virus replication. Other microRNAs exhibiting a similar expression pattern in resting and activated cells have been shown to directly target the HIV-1 genome. In this review we will discuss the resting state and the causes behind viral restriction in resting cells, with emphasis on the role of microRNAs. Full article
(This article belongs to the Special Issue Viruses and miRNAs)
Open AccessReview Structural Aspects of the Interaction of Dairy Phages with Their Host Bacteria
Viruses 2012, 4(9), 1410-1424; doi:10.3390/v4091410
Received: 13 July 2012 / Revised: 22 August 2012 / Accepted: 23 August 2012 / Published: 31 August 2012
Cited by 12 | PDF Full-text (986 KB) | HTML Full-text | XML Full-text
Abstract
Knowledge of phage-host interactions at a fundamental level is central to the design of rational strategies for the development of phage-resistant strains that may be applied in industrial settings. Phages infecting lactic acid bacteria, in particular Lactococcus lactis and Streptococcus thermophilus, negatively
[...] Read more.
Knowledge of phage-host interactions at a fundamental level is central to the design of rational strategies for the development of phage-resistant strains that may be applied in industrial settings. Phages infecting lactic acid bacteria, in particular Lactococcus lactis and Streptococcus thermophilus, negatively impact on dairy fermentation processes with serious economic implications. In recent years a wealth of information on structural protein assembly and topology has become available relating to phages infecting Escherichia coli, Bacillus subtilis and Lactococcus lactis, which act as models for structural analyses of dairy phages. In this review, we explore the role of model tailed phages, such as T4 and SPP1, in advancing our knowledge regarding interactions between dairy phages and their hosts. Furthermore, the potential of currently investigated dairy phages to in turn serve as model systems for this particular group of phages is discussed. Full article
(This article belongs to the Special Issue Recent Progress in Bacteriophage Research) Print Edition available
Open AccessReview Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses
Viruses 2012, 4(9), 1438-1476; doi:10.3390/v4091438
Received: 3 July 2012 / Revised: 10 August 2012 / Accepted: 22 August 2012 / Published: 3 September 2012
Cited by 40 | PDF Full-text (4444 KB) | HTML Full-text | XML Full-text
Abstract
The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade
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The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the current knowledge about immune evasion can be used to improve influenza A vaccination strategies. Full article
(This article belongs to the Special Issue Immune Evasion)
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Open AccessReview Mouse Models for Filovirus Infections
Viruses 2012, 4(9), 1477-1508; doi:10.3390/v4091477
Received: 11 July 2012 / Revised: 27 August 2012 / Accepted: 27 August 2012 / Published: 7 September 2012
Cited by 25 | PDF Full-text (905 KB) | HTML Full-text | XML Full-text
Abstract
The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF) in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs
[...] Read more.
The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF) in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (NHPs), guinea pigs and mice as animal models. NHPs appear to closely mirror filoviral HF in humans (based on limited clinical data), but only small numbers may be used in carefully regulated experiments; much research is therefore done in rodents. Because of their availability in large numbers and the existence of a wealth of reagents for biochemical and immunological testing, mice have become the preferred small animal model for filovirus research. Since the first experiments following the initial 1967 marburgvirus outbreak, wild-type or mouse-adapted viruses have been tested in immunocompetent or immunodeficient mice. In this paper, we review how these types of studies have been used to investigate the pathogenesis of filoviral disease, identify immune responses to infection and evaluate antiviral drugs and vaccines. We also discuss the strengths and weaknesses of murine models for filovirus research, and identify important questions for further study. Full article
(This article belongs to the Special Issue Advances in Filovirus Research 2012) Print Edition available
Open AccessReview Does Apoptosis Play a Role in Varicella Zoster Virus Latency and Reactivation?
Viruses 2012, 4(9), 1509-1514; doi:10.3390/v4091509
Received: 13 August 2012 / Revised: 5 September 2012 / Accepted: 6 September 2012 / Published: 11 September 2012
Cited by 6 | PDF Full-text (227 KB) | HTML Full-text | XML Full-text
Abstract
Varicella zoster virus (VZV) is an exclusively human highly neurotropic alphaherpesvirus. To date, VZV has been shown to induce apoptosis, primarily through the intrinsic pathway in different cell types, except for neurons in which the virus becomes latent. This review summarizes current studies
[...] Read more.
Varicella zoster virus (VZV) is an exclusively human highly neurotropic alphaherpesvirus. To date, VZV has been shown to induce apoptosis, primarily through the intrinsic pathway in different cell types, except for neurons in which the virus becomes latent. This review summarizes current studies of varicella-induced apoptosis in non‑neuronal cells. Future studies are proposed to determine whether apoptosis is terminated prematurely or even begins in neurons that are non-productively infected with VZV. Full article
(This article belongs to the Special Issue Modulation of Apoptosis by Viral Infection)
Open AccessReview Emaravirus: A Novel Genus of Multipartite, Negative Strand RNA Plant Viruses
Viruses 2012, 4(9), 1515-1536; doi:10.3390/v4091515
Received: 29 July 2012 / Revised: 22 August 2012 / Accepted: 22 August 2012 / Published: 12 September 2012
Cited by 24 | PDF Full-text (1161 KB) | HTML Full-text | XML Full-text
Abstract
Ringspot symptoms in European mountain ash (Sorbus aucuparia L.), fig mosaic, rose rosette, raspberry leaf blotch, pigeonpea sterility mosaic (Cajanus cajan) and High Plains disease of maize and wheat were found to be associated with viruses that share several characteristics.
[...] Read more.
Ringspot symptoms in European mountain ash (Sorbus aucuparia L.), fig mosaic, rose rosette, raspberry leaf blotch, pigeonpea sterility mosaic (Cajanus cajan) and High Plains disease of maize and wheat were found to be associated with viruses that share several characteristics. They all have single-stranded multipartite RNA genomes of negative orientation. In some cases, double membrane-bound virus-like particles of 80 to 200 nm in diameter were found in infected tissue. Furthermore, at least five of these viruses were shown to be vectored by eriophyid mites. Sequences of European mountain ash ringspot-associated virus (EMARaV), Fig mosaic virus (FMV), rose rosette virus (RRV), raspberry leaf blotch virus (RLBV), pigeonpea sterility mosaic virus and High Plains virus strongly support their potential phylogenetic relationship. Therefore, after characterization of EMARaV, the novel genus Emaravirus was established, and FMV was the second virus species assigned to this genus. The recently sequenced RRV and RLBV are supposed to be additional members of this new group of plant RNA viruses. Full article
(This article belongs to the Special Issue Plant Viruses)
Open AccessReview Contributions of Epstein–Barr Nuclear Antigen 1 (EBNA1) to Cell Immortalization and Survival
Viruses 2012, 4(9), 1537-1547; doi:10.3390/v4091537
Received: 19 July 2012 / Revised: 14 August 2012 / Accepted: 27 August 2012 / Published: 13 September 2012
Cited by 28 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
Epstein–Barr virus (EBV) immortalizes host cells as part of its latent mode of infection. As a result of this ability to promote cell proliferation and survival, EBV infection contributes to the development of several kinds of B-cell lymphomas and epithelial tumours. The EBV
[...] Read more.
Epstein–Barr virus (EBV) immortalizes host cells as part of its latent mode of infection. As a result of this ability to promote cell proliferation and survival, EBV infection contributes to the development of several kinds of B-cell lymphomas and epithelial tumours. The EBV Epstein–Barr nuclear antigen 1 (EBNA1) protein is the only EBV protein expressed in all EBV-associated tumours and plays multiple important roles in EBV latency. In addition to its well-studied roles in viral DNA replication, segregation and transcriptional activation, several studies have identified roles of EBNA1 in manipulating cellular processes that result in reduced apoptosis and increased cell survival. This review discusses these cellular effects of EBNA1 and mechanisms by which they occur. Full article
(This article belongs to the Special Issue Modulation of Apoptosis by Viral Infection)
Open AccessReview Host Cell Factors as Antiviral Targets in Arenavirus Infection
Viruses 2012, 4(9), 1569-1591; doi:10.3390/v4091569
Received: 17 August 2012 / Revised: 31 August 2012 / Accepted: 4 September 2012 / Published: 13 September 2012
Cited by 8 | PDF Full-text (760 KB) | HTML Full-text | XML Full-text
Abstract
Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of
[...] Read more.
Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. Since diverse host cell pathways and enzymes are used by RNA viruses to fulfill their replicative cycle, the targeting of a host process has turned an attractive antiviral approach in the last years for many unrelated virus types. This strategy has the additional benefit to reduce the serious challenge for therapy of RNA viruses to escape from drug effects through selection of resistant variants triggered by their high mutation rate. This article focuses on novel strategies to identify inhibitors for arenavirus therapy, analyzing the potential for antiviral developments of diverse host factors essential for virus infection. Full article
(This article belongs to the Special Issue Arenaviruses)
Open AccessReview Potential Vaccines and Post-Exposure Treatments for Filovirus Infections
Viruses 2012, 4(9), 1619-1650; doi:10.3390/v4091619
Received: 20 July 2012 / Revised: 31 August 2012 / Accepted: 4 September 2012 / Published: 20 September 2012
Cited by 32 | PDF Full-text (446 KB) | HTML Full-text | XML Full-text
Abstract
Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current
[...] Read more.
Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. Full article
(This article belongs to the Special Issue Advances in Filovirus Research 2012) Print Edition available
Open AccessReview Uncovering Viral Protein-Protein Interactions and their Role in Arenavirus Life Cycle
Viruses 2012, 4(9), 1651-1667; doi:10.3390/v4091651
Received: 8 August 2012 / Revised: 4 September 2012 / Accepted: 10 September 2012 / Published: 20 September 2012
Cited by 4 | PDF Full-text (620 KB) | HTML Full-text | XML Full-text
Abstract
The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded
[...] Read more.
The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA dependent-RNA polymerase (L protein) and requires viral RNA encapsidation by the Nucleoprotein. In addition to the role that the interaction between L and the Nucleoprotein may have in the replication process, polymerase activity appears to be modulated by the association between L and the small multifunctional Z protein. Z is also a structural component of the virions that plays an essential role in viral morphogenesis. Indeed, interaction of the Z protein with the Nucleoprotein is critical for genome packaging. Furthermore, current evidence suggests that binding between Z and the viral envelope glycoprotein complex is required for virion infectivity, and that Z homo-oligomerization is an essential step for particle assembly and budding. Efforts to understand the molecular basis of arenavirus life cycle have revealed important details on these viral protein-protein interactions that will be reviewed in this article. Full article
Open AccessReview Clinical Management of Filovirus-Infected Patients
Viruses 2012, 4(9), 1668-1686; doi:10.3390/v4091668
Received: 4 July 2012 / Revised: 10 September 2012 / Accepted: 11 September 2012 / Published: 20 September 2012
Cited by 34 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text
Abstract
Filovirus infection presents many unique challenges to patient management. Currently no approved treatments are available, and the recommendations for supportive care are not evidence based. The austere clinical settings in which patients often present and the sporadic and at times explosive nature of
[...] Read more.
Filovirus infection presents many unique challenges to patient management. Currently no approved treatments are available, and the recommendations for supportive care are not evidence based. The austere clinical settings in which patients often present and the sporadic and at times explosive nature of filovirus outbreaks have effectively limited the information available to evaluate potential management strategies. This review will summarize the management approaches used in filovirus outbreaks and provide recommendations for collecting the information necessary for evaluating and potentially improving patient outcomes in the future. Full article
(This article belongs to the Special Issue Advances in Filovirus Research 2012) Print Edition available
Open AccessReview Emerging Themes from EBV and KSHV microRNA Targets
Viruses 2012, 4(9), 1687-1710; doi:10.3390/v4091687
Received: 31 July 2012 / Revised: 22 August 2012 / Accepted: 3 September 2012 / Published: 21 September 2012
Cited by 25 | PDF Full-text (2594 KB) | HTML Full-text | XML Full-text
Abstract
EBV and KSHV are both gamma-herpesviruses which express multiple viral microRNAs. Various methods have been used to investigate the functions of these microRNAs, largely through identification of microRNA target genes. Surprisingly, these related viruses do not share significant sequence homology in their microRNAs.
[...] Read more.
EBV and KSHV are both gamma-herpesviruses which express multiple viral microRNAs. Various methods have been used to investigate the functions of these microRNAs, largely through identification of microRNA target genes. Surprisingly, these related viruses do not share significant sequence homology in their microRNAs. A number of reports have described functions of EBV and KSHV microRNA targets, however only three experimentally validated target genes have been shown to be targeted by microRNAs from both viruses. More sensitive methods to identify microRNA targets have predicted approximately 60% of host targets could be shared by EBV and KSHV microRNAs, but by targeting different sequences in the host targets. In this review, we explore the similarities of microRNA functions and targets of these related viruses. Full article
(This article belongs to the Special Issue Viruses and miRNAs)
Open AccessReview Human Leukocyte Antigen (HLA) Class I Down-Regulation by Human Immunodeficiency Virus Type 1 Negative Factor (HIV-1 Nef): What Might We Learn From Natural Sequence Variants?
Viruses 2012, 4(9), 1711-1730; doi:10.3390/v4091711
Received: 31 August 2012 / Revised: 18 September 2012 / Accepted: 21 September 2012 / Published: 24 September 2012
Cited by 10 | PDF Full-text (3083 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to
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HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine protein domains that are required for its immune evasion activities and to identify critical cellular co-factors, and our mechanistic understanding of this process is becoming more complete. This review highlights our current knowledge of Nef-mediated HLA class I down-regulation and places this work in the context of naturally occurring sequence variation in this protein. We argue that efforts to fully understand the critical role of Nef for HIV-1 pathogenesis will require greater analysis of patient-derived sequences to elucidate subtle differences in immune evasion activity that may alter clinical outcome. Full article
(This article belongs to the Special Issue Immune Evasion)
Open AccessReview Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?
Viruses 2012, 4(9), 1731-1752; doi:10.3390/v4091731
Received: 2 August 2012 / Revised: 1 September 2012 / Accepted: 17 September 2012 / Published: 24 September 2012
Cited by 16 | PDF Full-text (825 KB) | HTML Full-text | XML Full-text
Abstract
The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing
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The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy. Full article
(This article belongs to the Special Issue Immune Evasion)
Open AccessReview Diversity of Dicotyledenous-Infecting Geminiviruses and Their Associated DNA Molecules in Southern Africa, Including the South-West Indian Ocean Islands
Viruses 2012, 4(9), 1753-1791; doi:10.3390/v4091753
Received: 3 August 2012 / Revised: 4 September 2012 / Accepted: 5 September 2012 / Published: 24 September 2012
Cited by 8 | PDF Full-text (1189 KB) | HTML Full-text | XML Full-text
Abstract
The family Geminiviridae comprises a group of plant-infecting circular ssDNA viruses that severely constrain agricultural production throughout the temperate regions of the world, and are a particularly serious threat to food security in sub-Saharan Africa. While geminiviruses exhibit considerable diversity in terms of
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The family Geminiviridae comprises a group of plant-infecting circular ssDNA viruses that severely constrain agricultural production throughout the temperate regions of the world, and are a particularly serious threat to food security in sub-Saharan Africa. While geminiviruses exhibit considerable diversity in terms of their nucleotide sequences, genome structures, host ranges and insect vectors, the best characterised and economically most important of these viruses are those in the genus Begomovirus. Whereas begomoviruses are generally considered to be either monopartite (one ssDNA component) or bipartite (two circular ssDNA components called DNA-A and DNA-B), many apparently monopartite begomoviruses are associated with additional subviral ssDNA satellite components, called alpha- (DNA-as) or betasatellites (DNA-βs). Additionally, subgenomic molecules, also known as defective interfering (DIs) DNAs that are usually derived from the parent helper virus through deletions of parts of its genome, are also associated with bipartite and monopartite begomoviruses. The past three decades have witnessed the emergence and diversification of various new begomoviral species and associated DI DNAs, in southern Africa, East Africa, and proximal Indian Ocean islands, which today threaten important vegetable and commercial crops such as, tobacco, cassava, tomato, sweet potato, and beans. This review aims to describe what is known about these viruses and their impacts on sustainable production in this sensitive region of the world. Full article
(This article belongs to the Special Issue Plant Viruses)

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