Viruses

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Open AccessLetter

Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

by Jens H. Kuhn, Kristian G. Andersen, Sylvain Baize, Yīmíng Bào, Sina Bavari, Nicolas Berthet, Olga Blinkova, J. Rodney Brister, Anna N. Clawson, Joseph Fair, Martin Gabriel, Robert F. Garry, Stephen K. Gire, Augustine Goba, Jean-Paul Gonzalez, Stephan Günther, Christian T. Happi, Peter B. Jahrling, Jimmy Kapetshi, Gary Kobinger, Jeffrey R. Kugelman, Eric M. Leroy, Gael Darren Maganga, Placide K. Mbala, Lina M. Moses, Jean-Jacques Muyembe-Tamfum, Magassouba N'Faly, Stuart T. Nichol, Sunday A. Omilabu, Gustavo Palacios, Daniel J. Park, Janusz T. Paweska, Sheli R. Radoshitzky, Cynthia A. Rossi, Pardis C. Sabeti, John S. Schieffelin, Randal J. Schoepp, Rachel Sealfon, Robert Swanepoel, Jonathan S. Towner, Jiro Wada, Nadia Wauquier, Nathan L. Yozwiak and Pierre Formenty Show full author list Hide full author list

Viruses 2014, 6(11), 4760-4799; https://doi.org/10.3390/v6114760 - 24 Nov 2014

Cited by 76 | Viewed by 20383

Abstract

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all [...] Read more.

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. Full article

(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)

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Open AccessReview

KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

by Natacha Coen, Sophie Duraffour, Robert Snoeck and Graciela Andrei

Viruses 2014, 6(11), 4731-4759; https://doi.org/10.3390/v6114731 - 24 Nov 2014

Cited by 50 | Viewed by 11046

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 efficacious. [...] 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)

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Open AccessReview

Flavivirus-Mosquito Interactions

by Yan-Jang S. Huang, Stephen Higgs, Kate McElroy Horne and Dana L. Vanlandingham

Viruses 2014, 6(11), 4703-4730; https://doi.org/10.3390/v6114703 - 24 Nov 2014

Cited by 125 | Viewed by 15302

Abstract

The Flavivirus genus is in the family Flaviviridae and is comprised of more than 70 viruses. These viruses have a broad geographic range, circulating on every continent except Antarctica. Mosquito-borne flaviviruses, such as yellow fever virus, dengue virus serotypes 1–4, Japanese encephalitis virus, [...] Read more.

The Flavivirus genus is in the family Flaviviridae and is comprised of more than 70 viruses. These viruses have a broad geographic range, circulating on every continent except Antarctica. Mosquito-borne flaviviruses, such as yellow fever virus, dengue virus serotypes 1–4, Japanese encephalitis virus, and West Nile virus are responsible for significant human morbidity and mortality in affected regions. This review focuses on what is known about flavivirus-mosquito interactions and presents key data collected from the field and laboratory-based molecular and ultrastructural evaluations. Full article

(This article belongs to the Special Issue Interactions between Arboviruses and Arthropod Vectors)

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Open AccessReview

Hepatitis B Virus HBx Protein Interactions with the Ubiquitin Proteasome System

by Marissa M. Minor and Betty L. Slagle

Viruses 2014, 6(11), 4683-4702; https://doi.org/10.3390/v6114683 - 24 Nov 2014

Cited by 58 | Viewed by 11767

Abstract

The hepatitis B virus (HBV) causes acute and chronic hepatitis, and the latter is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV encodes a 17-kDa regulatory protein, HBx, which is required for virus replication. Although the precise contribution(s) of [...] Read more.

The hepatitis B virus (HBV) causes acute and chronic hepatitis, and the latter is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV encodes a 17-kDa regulatory protein, HBx, which is required for virus replication. Although the precise contribution(s) of HBx to virus replication is unknown, many viruses target cellular pathways to create an environment favorable for virus replication. The ubiquitin proteasome system (UPS) is a major conserved cellular pathway that controls several critical processes in the cell by regulating the levels of proteins involved in cell cycle, DNA repair, innate immunity, and other processes. We summarize here the interactions of HBx with components of the UPS, including the CUL4 adaptor DDB1, the cullin regulatory complex CSN, and the 26S proteasome. Understanding how these protein interactions benefit virus replication remains a challenge due to limited models in which to study HBV replication. However, studies from other viral systems that similarly target the UPS provide insight into possible strategies used by HBV. Full article

(This article belongs to the Special Issue Viruses and the Ubiquitin/Proteasome System)

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Open AccessArticle

Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates

by Travis K. Warren, John C. Trefry, Shannon T. Marko, Taylor B. Chance, Jay B. Wells, William D. Pratt, Joshua C. Johnson, Eric M. Mucker, Sarah L. Norris, Mark Chappell, John M. Dye and Anna N. Honko

Viruses 2014, 6(11), 4666-4682; https://doi.org/10.3390/v6114666 - 24 Nov 2014

Cited by 21 | Viewed by 9736

Abstract

Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy [...] Read more.

Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts. Full article

(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)

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Open AccessCorrection

Correction: Taliaferro, L. et al. Evaluation of the Broad-Range PCR-Electrospray Ionization Mass Spectrometry (PCR/ESI-MS) System and Virus Microarrays for Virus Detection. Viruses 2014, 6, 1876-1896

by Lanyn P. Taliaferro, Teresa A. Galvin, Hailun Ma, Syed Shaheduzzaman, Dhanya K. Williams, Dustin R. Glasner and Arifa S. Khan

Viruses 2014, 6(11), 4664-4665; https://doi.org/10.3390/v6114664 - 24 Nov 2014

Viewed by 4569

Abstract

We have noted some inaccuracies in Table 1 and Table 2 of our article “Evaluation of the Broad-Range PCR-Electrospray Ionization Mass Spectrometry (PCR/ESI-MS) System and Virus Microarrays for Virus Detection” (Viruses 2014, 6, 1876–1896) [1].[...] Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Chikungunya Virus–Vector Interactions

by Lark L. Coffey, Anna-Bella Failloux and Scott C. Weaver

Viruses 2014, 6(11), 4628-4663; https://doi.org/10.3390/v6114628 - 24 Nov 2014

Cited by 125 | Viewed by 20444

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding [...] Read more.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed. Full article

(This article belongs to the Special Issue Interactions between Arboviruses and Arthropod Vectors)

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Open AccessReview

Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

by Adjimon Gatien Lokossou, Caroline Toudic and Benoit Barbeau

Viruses 2014, 6(11), 4609-4627; https://doi.org/10.3390/v6114609 - 24 Nov 2014

Cited by 79 | Viewed by 12714

Abstract

Human endogenous retroviruses (ERVs) represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs), a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of [...] Read more.

Human endogenous retroviruses (ERVs) represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs), a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env) proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessReview

HIV Eradication: Combinatorial Approaches to Activate Latent Viruses

by Elisa De Crignis and Tokameh Mahmoudi

Viruses 2014, 6(11), 4581-4608; https://doi.org/10.3390/v6114581 - 21 Nov 2014

Cited by 13 | Viewed by 7434

Abstract

The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due [...] Read more.

The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due to the presence of a reservoir of latent HIV infected cells, which persist in the presence of c-ART. Recently, pharmaceutical approaches have focused on the development of molecules able to induce HIV-1 replication from latently infected cells in order to render them susceptible to viral cytopathic effects and host immune responses. Alternative pathways and transcription complexes function to regulate the activity of the HIV promoter and might serve as molecular targets for compounds to activate latent HIV. A combined therapy coupling various depressors and activators will likely be the most effective in promoting HIV replication while avoiding pleiotropic effects at the cellular level. Moreover, in light of differences among HIV subtypes and variability in integration sites, the combination of multiple agents targeting multiple pathways will increase likelihood of therapeutic effectiveness and prevent mutational escape. This review provides an overview of the mechanisms that can be targeted to induce HIV activation focusing on potential combinatorial approaches. Full article

(This article belongs to the Special Issue HIV Latency)

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Open AccessReview

Role of Host MicroRNAs in Kaposi’s Sarcoma-Associated Herpesvirus Pathogenesis

by Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss and Lu Dai

Viruses 2014, 6(11), 4571-4580; https://doi.org/10.3390/v6114571 - 21 Nov 2014

Cited by 16 | Viewed by 6423

Abstract

MicroRNAs (miRNAs) are small non-coding RNA species that can bind to both untranslated and coding regions of target mRNAs, causing their degradation or post-transcriptional modification. Currently, over 2500 miRNAs have been identified in the human genome. Burgeoning evidence suggests that dysregulation of human [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNA species that can bind to both untranslated and coding regions of target mRNAs, causing their degradation or post-transcriptional modification. Currently, over 2500 miRNAs have been identified in the human genome. Burgeoning evidence suggests that dysregulation of human miRNAs can play a role in the pathogenesis of a variety of diseases, including cancer. In contrast, only a small subset of human miRNAs has been functionally validated in the pathogenesis of oncogenic viruses, in particular, Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV is the etiologic agent of several human cancers, such as primary effusion lymphoma (PEL) and Kaposi’s sarcoma (KS), which are mostly seen in acquired immune deficiency syndrome (AIDS) patients or other immuno-suppressed subpopulation. This review summarizes recent literature outlining mechanisms for KSHV/viral proteins regulation of cellular miRNAs contributing to viral pathogenesis, as well as recent findings about the unique signature of miRNAs induced by KSHV infection or KSHV-related malignancies. Full article

(This article belongs to the Special Issue Tumour Viruses)

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Open AccessReview

Structure, Function and Dynamics in Adenovirus Maturation

by Walter F. Mangel and Carmen San Martín

Viruses 2014, 6(11), 4536-4570; https://doi.org/10.3390/v6114536 - 21 Nov 2014

Cited by 99 | Viewed by 13305

Abstract

Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and [...] Read more.

Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core is more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. Finally, possible roles for maturation of the terminal protein are discussed. Full article

(This article belongs to the Special Issue Virus Maturation)

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Open AccessReview

Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

by Samia Hannaoui, Su Yeon Shim, Yo Ching Cheng, Erica Corda and Sabine Gilch

Viruses 2014, 6(11), 4505-4535; https://doi.org/10.3390/v6114505 - 20 Nov 2014

Cited by 29 | Viewed by 11673

Abstract

Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrP^Sc, an aberrantly folded isoform of the cellular prion protein PrP^C, in the brains of affected individuals. PrP^C is [...] Read more.

Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrP^Sc, an aberrantly folded isoform of the cellular prion protein PrP^C, in the brains of affected individuals. PrP^C is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrP^C and prevents PrP^Sc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. Full article

(This article belongs to the Section Prions)

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Open AccessReview

Mosquito Immunity against Arboviruses

by Shuzhen Sim, Natapong Jupatanakul and George Dimopoulos

Viruses 2014, 6(11), 4479-4504; https://doi.org/10.3390/v6114479 - 19 Nov 2014

Cited by 128 | Viewed by 13647

Abstract

Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control [...] Read more.

Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. Here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundamental cellular processes such as apoptosis and autophagy, and arboviral suppression of mosquito defense mechanisms. This knowledge provides insights into co-evolutionary processes between vector and virus and also lays the groundwork for the development of novel arbovirus control strategies that target the mosquito vector. Full article

(This article belongs to the Special Issue Interactions between Arboviruses and Arthropod Vectors)

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Open AccessArticle

Analysis of Adaptive Evolution in Lyssavirus Genomes Reveals Pervasive Diversifying Selection during Species Diversification

by Carolina M. Voloch, Renata T. Capellão, Beatriz Mello and Carlos G. Schrago

Viruses 2014, 6(11), 4465-4478; https://doi.org/10.3390/v6114465 - 19 Nov 2014

Cited by 4 | Viewed by 6456

Abstract

Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive [...] Read more.

Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G), RNA-dependent RNA polymerase (L) and polymerase (P) genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the L gene were found to be associated with the early diversification of phylogroups. A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Host Control of Insect Endogenous Retroviruses: Small RNA Silencing and Immune Response

by Marie Fablet

Viruses 2014, 6(11), 4447-4464; https://doi.org/10.3390/v6114447 - 18 Nov 2014

Cited by 11 | Viewed by 8830

Abstract

Endogenous retroviruses are relics of ancient infections from retroviruses that managed to integrate into the genome of germline cells and remained vertically transmitted from parent to progeny. Subsequent to the endogenization process, these sequences can move and multiply in the host genome, which [...] Read more.

Endogenous retroviruses are relics of ancient infections from retroviruses that managed to integrate into the genome of germline cells and remained vertically transmitted from parent to progeny. Subsequent to the endogenization process, these sequences can move and multiply in the host genome, which can have deleterious consequences and disturb genomic stability. Natural selection favored the establishment of silencing pathways that protect host genomes from the activity of endogenous retroviruses. RNA silencing mechanisms are involved, which utilize piRNAs. The response to exogenous viral infections uses siRNAs, a class of small RNAs that are generated via a distinct biogenesis pathway from piRNAs. However, interplay between both pathways has been identified, and interactions with anti-bacterial and anti-fungal immune responses are also suspected. This review focuses on Diptera (Arthropods) and intends to compile pieces of evidence showing that the RNA silencing pathway of endogenous retrovirus regulation is not independent from immunity and the response to infections. This review will consider the mechanisms that allow the lasting coexistence of viral sequences and host genomes from an evolutionary perspective. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessShort Communication

Molecular Markers of Influenza B Lineages and Clades

by Rosaria Arvia, Fabiana Corcioli, Federica Pierucci and Alberta Azzi

Viruses 2014, 6(11), 4437-4446; https://doi.org/10.3390/v6114437 - 18 Nov 2014

Cited by 17 | Viewed by 5790

Abstract

Co-circulation of two influenza B virus lineages, B/Yamagata and B/Victoria, has been recognized since the late 1980s. The assessment of the prevalent lineage and the group of viruses in circulation is of importance in order to decide on the vaccine composition and evaluate [...] Read more.

Co-circulation of two influenza B virus lineages, B/Yamagata and B/Victoria, has been recognized since the late 1980s. The assessment of the prevalent lineage and the group of viruses in circulation is of importance in order to decide on the vaccine composition and evaluate its efficacy. The molecular characterization of influenza B viruses in circulation has been the aim of this study; this was approached by identifying and locating nucleotide substitutions in the influenza B virus hemagglutinin (HA) and neuraminidase (NA), specific for the lineage and/or clade. By the alignment of 3456 sequences from the influenza GISAID EpiFlu database, a high number of lineage- and group-specific nucleotide positions have been observed in the HA gene, but not in the NA gene. Additionally, an RT-PCR method has been developed, applicable directly to clinical specimens, which amplifies a short HA region that includes a group of unique molecular signatures. Twenty eight influenza B virus-positive respiratory specimens, collected in Tuscany in the seasons 2012–2013 and 2013–2014, were analyzed. The results revealed two clearly distinguishable patterns: one, more frequent, was characterized by all of the nucleotide changes associated with the B/Yamagata lineage (in most cases of Group 2), whereas the other exhibited all of the changes associated with the B/Victoria lineage. It can be concluded that the analysis of this short HA sequence can permit a rapid, highly sensitive determination of influenza B virus lineages and clades. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Genetic Diversity of PRRS Virus Collected from Air Samples in Four Different Regions of Concentrated Swine Production during a High Incidence Season

by Barbara Brito, Scott Dee, Spencer Wayne, Julio Alvarez and Andres Perez

Viruses 2014, 6(11), 4424-4436; https://doi.org/10.3390/v6114424 - 14 Nov 2014

Cited by 22 | Viewed by 7092

Abstract

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most relevant swine diseases in the US, costing the industry millions of dollars per year. Unfortunately, disease control is difficult because of the virus dynamics, as PRRS virus (PRRSV) can be transmitted by [...] Read more.

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most relevant swine diseases in the US, costing the industry millions of dollars per year. Unfortunately, disease control is difficult because of the virus dynamics, as PRRS virus (PRRSV) can be transmitted by air between farms, especially, in regions with high density of swine operations. While long distance airborne transport of PRRSV has been reported, there is little information regarding the dynamics of PRRSV airborne challenge in concentrated regions. The objective of this study was to describe the frequency of detection, dose and diversity of PRRSV in air samples collected across four concentrated production regions during the PRRS-high risk season in the Midwestern US (October–December) in 2012. Between 29% and 42% of the air samples were positive in all four sampling sites. Sequencing of the recovered virus showed a wide diversity of field and vaccine variants. Higher frequency, dose, and diversity of PRRSV were observed in air at locations with higher pig density. These findings suggest that regional spread of PRRSV due to aerosol transmission of PRRSV represents a significant risk to susceptible herds in concentrated regions of domestic pig production where PRRSV is endemic. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessCorrection

Correction: Forrester, N.L.; Coffey, L.L.; Weaver, S.C. Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission. Viruses 2014, 6, 3991–4004

by Naomi L. Forrester, Lark L. Coffey and Scott C. Weaver

Viruses 2014, 6(11), 4422-4423; https://doi.org/10.3390/v6114422 - 14 Nov 2014

Viewed by 4873

Abstract

In the original manuscript, Forrester, N.L.; Coffey, L.L.; Weaver, S.C. Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission. Viruses 2014, 6, 3991–4004, Figure 1 contains an error, the third bottle was absent from the figure:[...] Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Assessing Proteinase K Resistance of Fish Prion Proteins in a Scrapie-Infected Mouse Neuroblastoma Cell Line

by Evgenia Salta, Eirini Kanata, Christos A. Ouzounis, Sabine Gilch, Hermann Schätzl and Theodoros Sklaviadis

Viruses 2014, 6(11), 4398-4421; https://doi.org/10.3390/v6114398 - 13 Nov 2014

Cited by 5 | Viewed by 7372

Abstract

The key event in prion pathogenesis is the structural conversion of the normal cellular protein, PrP^C, into an aberrant and partially proteinase K resistant isoform, PrP^Sc. Since the minimum requirement for a prion disease phenotype is the expression of [...] Read more.

The key event in prion pathogenesis is the structural conversion of the normal cellular protein, PrP^C, into an aberrant and partially proteinase K resistant isoform, PrP^Sc. Since the minimum requirement for a prion disease phenotype is the expression of endogenous PrP in the host, species carrying orthologue prion genes, such as fish, could in theory support prion pathogenesis. Our previous work has demonstrated the development of abnormal protein deposition in sea bream brain, following oral challenge of the fish with natural prion infectious material. In this study, we used a prion-infected mouse neuroblastoma cell line for the expression of three different mature fish PrP proteins and the evaluation of the resistance of the exogenously expressed proteins to proteinase K treatment (PK), as an indicator of a possible prion conversion. No evidence of resistance to PK was detected for any of the studied recombinant proteins. Although not indicative of an absolute inability of the fish PrPs to structurally convert to pathogenic isoforms, the absence of PK-resistance may be due to supramolecular and conformational differences between the mammalian and piscine PrPs. Full article

(This article belongs to the Special Issue Recent Developments in the Prion Field)

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Open AccessReview

Bunyavirus-Vector Interactions

by Kate McElroy Horne and Dana L. Vanlandingham

Viruses 2014, 6(11), 4373-4397; https://doi.org/10.3390/v6114373 - 13 Nov 2014

Cited by 51 | Viewed by 11473

Abstract

The Bunyaviridae family is comprised of more than 350 viruses, of which many within the Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus genera are significant human or agricultural pathogens. The viruses within the Orthobunyavirus, Nairovirus, and Phlebovirus genera [...] Read more.

The Bunyaviridae family is comprised of more than 350 viruses, of which many within the Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus genera are significant human or agricultural pathogens. The viruses within the Orthobunyavirus, Nairovirus, and Phlebovirus genera are transmitted by hematophagous arthropods, such as mosquitoes, midges, flies, and ticks, and their associated arthropods not only serve as vectors but also as virus reservoirs in many cases. This review presents an overview of several important emerging or re-emerging bunyaviruses and describes what is known about bunyavirus-vector interactions based on epidemiological, ultrastructural, and genetic studies of members of this virus family. Full article

(This article belongs to the Special Issue Interactions between Arboviruses and Arthropod Vectors)

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Open AccessArticle

Anti-Glycoprotein G Antibodies of Herpes Simplex Virus 2 Contribute to Complete Protection after Vaccination in Mice and Induce Antibody-Dependent Cellular Cytotoxicity and Complement-Mediated Cytolysis

by Staffan Görander, Maria Ekblad, Tomas Bergström and Jan-Åke Liljeqvist

Viruses 2014, 6(11), 4358-4372; https://doi.org/10.3390/v6114358 - 12 Nov 2014

Cited by 18 | Viewed by 6786

Abstract

We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 [...] Read more.

We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1) and IgG2 antibodies were detected and re-stimulated splenic CD4⁺ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis (ACMC) activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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Open AccessShort Communication

Genetic Characterization of Goutanap Virus, a Novel Virus Related to Negeviruses, Cileviruses and Higreviruses

by René Kallies, Anne Kopp, Florian Zirkel, Alejandro Estrada, Thomas R. Gillespie, Christian Drosten and Sandra Junglen

Viruses 2014, 6(11), 4346-4357; https://doi.org/10.3390/v6114346 - 12 Nov 2014

Cited by 56 | Viewed by 8930

Abstract

Pools of mosquitoes collected in Côte d’Ivoire and Mexico were tested for cytopathic effects on the mosquito cell line C6/36. Seven pools induced strong cytopathic effects after one to five days post infection and were further investigated by deep sequencing. The genomes of [...] Read more.

Pools of mosquitoes collected in Côte d’Ivoire and Mexico were tested for cytopathic effects on the mosquito cell line C6/36. Seven pools induced strong cytopathic effects after one to five days post infection and were further investigated by deep sequencing. The genomes of six virus isolates from Côte d’Ivoire showed pairwise nucleotide identities of ~99% among each other and of 56%–60% to Dezidougou virus and Wallerfield virus, two insect-specific viruses belonging to the proposed new taxon Negevirus. The novel virus was tentatively named Goutanap virus. The isolate derived from the Mexican mosquitoes showed 95% pairwise identity to Piura virus and was suggested to be a strain of Piura virus, named C6.7-MX-2008. Phylogenetic inferences based on a concatenated alignment of the methyltransferase, helicase, and RNA-dependent RNA polymerase domains showed that the new taxon Negevirus formed two monophyletic clades, named Nelorpivirus and Sandewavirus after the viruses grouping in these clades. Branch lengths separating these clades were equivalent to those of the related genera Cilevirus, Higrevirus and Blunervirus, as well as to those within the family Virgaviridae. Genetic distances and phylogenetic analyses suggest that Nelorpivirus and Sandewavirus might form taxonomic groups on genus level that may define alone or together with Cilevirus, Higrevirus and Blunervirus a viral family. Full article

(This article belongs to the Special Issue Impact of the Insect Microbiome on Arbovirus Transmission)

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Open AccessArticle

CMV-Promoter Driven Codon-Optimized Expression Alters the Assembly Type and Morphology of a Reconstituted HERV-K(HML-2)

by Oliver Hohn, Kirsten Hanke, Veronika Lausch, Anja Zimmermann, Saeed Mostafa and Norbert Bannert

Viruses 2014, 6(11), 4332-4345; https://doi.org/10.3390/v6114332 - 11 Nov 2014

Cited by 3 | Viewed by 8202

Abstract

The HERV-K(HML-2) family contains the most recently integrated and best preserved endogenized proviral sequences in the human genome. All known elements have nevertheless been subjected to mutations or deletions that render expressed particles non-infectious. Moreover, these post-insertional mutations hamper the analysis of the [...] Read more.

The HERV-K(HML-2) family contains the most recently integrated and best preserved endogenized proviral sequences in the human genome. All known elements have nevertheless been subjected to mutations or deletions that render expressed particles non-infectious. Moreover, these post-insertional mutations hamper the analysis of the general biological properties of this ancient virus family. The expression of consensus sequences and sequences of elements with reverted post-insertional mutations has therefore been very instrumental in overcoming this limitation. We investigated the particle morphology of a recently reconstituted HERV-K113 element termed oriHERV-K113 using thin-section electron microscopy (EM) and could demonstrate that strong overexpression by substitution of the 5'LTR for a CMV promoter and partial codon optimization altered the virus assembly type and morphology. This included a conversion from the regular C-type to an A-type morphology with a mass of cytoplasmic immature cores tethered to the cell membrane and the membranes of vesicles. Overexpression permitted the release and maturation of virions but reduced the envelope content. A weaker boost of virus expression by Staufen-1 was not sufficient to induce these morphological alterations. Full article

(This article belongs to the Special Issue Electron Microscopy in Virus Diagnostics and Research)

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Open AccessReview

Mosquito-Borne Viruses and Suppressors of Invertebrate Antiviral RNA Silencing

by Scott T. O'Neal, Glady Hazitha Samuel, Zach N. Adelman and Kevin M. Myles

Viruses 2014, 6(11), 4314-4331; https://doi.org/10.3390/v6114314 - 11 Nov 2014

Cited by 23 | Viewed by 8244

Abstract

The natural maintenance cycles of many mosquito-borne viruses require establishment of persistent non-lethal infections in the invertebrate host. While the mechanisms by which this occurs are not well understood, antiviral responses directed by small RNAs are important in modulating the pathogenesis of viral [...] Read more.

The natural maintenance cycles of many mosquito-borne viruses require establishment of persistent non-lethal infections in the invertebrate host. While the mechanisms by which this occurs are not well understood, antiviral responses directed by small RNAs are important in modulating the pathogenesis of viral infections in disease vector mosquitoes. In yet another example of an evolutionary arms race between host and pathogen, some plant and insect viruses have evolved to encode suppressors of RNA silencing (VSRs). Whether or not mosquito-borne viral pathogens encode VSRs has been the subject of debate. While at first there would seem to be little evolutionary benefit to mosquito-borne viruses encoding proteins or sequences that strongly interfere with RNA silencing, we present here a model explaining how the expression of VSRs by these viruses in the vector might be compatible with the establishment of persistence. We also discuss the challenges associated with interrogating these viruses for the presence of suppressor proteins or sequences, as well as the candidates that have been identified in the genomes of mosquito-borne pathogens thus far. Full article

(This article belongs to the Special Issue Interactions between Arboviruses and Arthropod Vectors)

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Open AccessReview

The Insect Microbiome Modulates Vector Competence for Arboviruses

by Natapong Jupatanakul, Shuzhen Sim and George Dimopoulos

Viruses 2014, 6(11), 4294-4313; https://doi.org/10.3390/v6114294 - 11 Nov 2014

Cited by 135 | Viewed by 12051

Abstract

Diseases caused by arthropod-borne viruses (arboviruses), such as Dengue, West Nile, and Chikungunya, constitute a major global health burden and are increasing in incidence and geographic range. The natural microbiota of insect vectors influences various aspects of host biology, such as nutrition, reproduction, [...] Read more.

Diseases caused by arthropod-borne viruses (arboviruses), such as Dengue, West Nile, and Chikungunya, constitute a major global health burden and are increasing in incidence and geographic range. The natural microbiota of insect vectors influences various aspects of host biology, such as nutrition, reproduction, metabolism, and immunity, and recent studies have highlighted the ability of insect-associated bacteria to reduce vector competence for arboviruses and other pathogens. This reduction can occur through mechanisms, such as immune response activation, resource competition, or the production of anti-viral molecules. Studying the interactions between insect vectors and their microbiota is an important step toward developing alternative strategies for arbovirus transmission control. Full article

(This article belongs to the Special Issue Impact of the Insect Microbiome on Arbovirus Transmission)

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Open AccessArticle

Japanese Encephalitis Virus Upregulates the Expression of SOCS3 in Mouse Brain and Raw264.7 Cells

by Xiangmin Li, Qiaoyan Zhu, Qishu Cao, Huanchun Chen and Ping Qian

Viruses 2014, 6(11), 4280-4293; https://doi.org/10.3390/v6114280 - 10 Nov 2014

Cited by 10 | Viewed by 7172

Abstract

Japanese encephalitis virus (JEV) is one of the pathogens that can invade the central nervous system, causing acute infection and inflammation of brain. SOCS3 protein plays a vital role in immune processes and inflammation of the central nervous system. In this study, Raw264.7 [...] Read more.

Japanese encephalitis virus (JEV) is one of the pathogens that can invade the central nervous system, causing acute infection and inflammation of brain. SOCS3 protein plays a vital role in immune processes and inflammation of the central nervous system. In this study, Raw264.7 cells and suckling mice were infected with JEV, and SOCS3 expression was analyzed by the gene expression profile, semiquantitative RT-PCR, qRT-PCR, immunohistochemistry (IHC) and Western blot. Results indicated that 520 genes were found to be differentially expressed (fold change ≥ 2.0, p < 0.05) in total. The differentially regulated genes were involved in biological processes, such as stimulus response, biological regulation and immune system processes. JEV early infection could induce SOCS3 expression, upregulating both the mRNA and protein levels in Raw264.7 cells in a time-dependent manner. The SOCS3 expression was much lower in Raw264.7 cells infected with inactivated JEV than wild-type JEV. In vivo, SOCS3 protein was also found to upregulate the expression of mRNA and protein in JEV-infected mouse brain. Taken together, our data showed that JEV early infection could induce the upregulation of SOCS3 expression, both in vitro and in vivo, providing the basic theoretical foundation for future research on the invasion mechanism of JEV. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

A Unique Evolution of the S2 Gene of Equine Infectious Anemia Virus in Hosts Correlated with Particular Infection Statuses

by Xue-Feng Wang, Shuai Wang, Qiang Liu, Yue-Zhi Lin, Cheng Du, Yan-Dong Tang, Lei Na, Xiaojun Wang and Jian-Hua Zhou

Viruses 2014, 6(11), 4265-4279; https://doi.org/10.3390/v6114265 - 10 Nov 2014

Cited by 2 | Viewed by 5749

Abstract

Equine infectious anemia virus (EIAV) is a member of the Lentivirus genus in the Retroviridae family that exhibits a genomic structure similar to that of HIV-1. The S2 accessory proteins play important roles in viral replication in vivo and in viral pathogenicity; however, [...] Read more.

Equine infectious anemia virus (EIAV) is a member of the Lentivirus genus in the Retroviridae family that exhibits a genomic structure similar to that of HIV-1. The S2 accessory proteins play important roles in viral replication in vivo and in viral pathogenicity; however, studies on S2 evolution in vivo are limited. This study analyzed the evolutionary characteristics of the S2 gene of a pathogenic EIAV strain, EIAV_LN40, in four experimentally infected horses. The results demonstrated that 14.7% (10 of 68 residues) of the stable amino acid mutations occurred longitudinally in S2 during a 150-day infection period. Further analysis revealed that six of the ten mutated residues were positively selected during the infection. Alignment and phylogenetic analyses showed that the S2 gene sequences of viruses isolated from the infected horses at the early stage of EIAV_LN40 infection were highly homologous and similar to the vaccine-specific sequence. The S2 gene variants isolated from the febrile episodes and late phase of infection became homologous to the S2 gene sequence of the inoculating EIAV_LN40 strain. Our results indicate that the S2 gene evolves in diversity and divergence in vivo in different stages of EIAV infection and that this evolution correlates with the pathogenicity of the virus. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessEssay

Twenty Years of KSHV

by Yuan Chang and Patrick Moore

Viruses 2014, 6(11), 4258-4264; https://doi.org/10.3390/v6114258 - 7 Nov 2014

Cited by 28 | Viewed by 6610

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 over [...] 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)

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Open AccessArticle

Apple Latent Spherical Virus Vector as Vaccine for the Prevention and Treatment of Mosaic Diseases in Pea, Broad Bean, and Eustoma Plants by Bean Yellow Mosaic Virus

by Nozomi Satoh, Tatsuya Kon, Noriko Yamagishi, Tsubasa Takahashi, Tomohide Natsuaki and Nobuyuki Yoshikawa

Viruses 2014, 6(11), 4242-4257; https://doi.org/10.3390/v6114242 - 7 Nov 2014

Cited by 14 | Viewed by 9087

Abstract

We investigated the protective effects of a viral vector based on an Apple latent spherical virus (ALSV) harboring a segment of the Bean yellow mosaic virus (BYMV) genome against mosaic diseases in pea, broad bean, and eustoma plants caused by BYMV infection. [...] Read more.

We investigated the protective effects of a viral vector based on an Apple latent spherical virus (ALSV) harboring a segment of the Bean yellow mosaic virus (BYMV) genome against mosaic diseases in pea, broad bean, and eustoma plants caused by BYMV infection. In pea plants pre-inoculated with the ALSV vaccine and challenge inoculated with BYMV expressing green fluorescence protein, BYMV multiplication occurred in inoculated leaves, but was markedly inhibited in the upper leaves. No mosaic symptoms due to BYMV infection were observed in the challenged plants pre-inoculated with the ALSV vaccine. Simultaneous inoculation with the ALSV vaccine and BYMV also prevented mosaic symptoms in broad bean and eustoma plants, and BYMV accumulation was strongly inhibited in the upper leaves of plants treated with the ALSV vaccine. Pea and eustoma plants were pre-inoculated with BYMV followed by inoculation with the ALSV vaccine to investigate the curative effects of the ALSV vaccine. In both plant species, recovery from mosaic symptoms was observed in upper leaves and BYMV accumulation was inhibited in leaves developing post-ALSV vaccination. These results show that ALSV vaccination not only prevents mosaic diseases in pea, broad bean, and eustoma, but that it is also effective in curing these diseases. Full article

(This article belongs to the Special Issue Advances in Gene Technology and Resistance to Viruses)

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Open AccessReview

Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

by Moheshwarnath Issur and Matthias Götte

Viruses 2014, 6(11), 4227-4241; https://doi.org/10.3390/v6114227 - 6 Nov 2014

Cited by 37 | Viewed by 8885

Abstract

Direct-acting antivirals (DAAs) have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in [...] Read more.

Direct-acting antivirals (DAAs) have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding. Full article

(This article belongs to the Special Issue HIV Drug Resistance)

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Viruses, Volume 6, Issue 11 (November 2014) – 35 articles , Pages 4140-4799

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