Viruses

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Open AccessReview

H5N1 Virus Evolution in Europe—An Updated Overview

by Giovanni Cattoli, Alice Fusaro, Isabella Monne and Ilaria Capua

Viruses 2009, 1(3), 1351-1363; https://doi.org/10.3390/v1031351 - 23 Dec 2009

Cited by 32 | Viewed by 11775

Since its emergence in South East Asia in 2003, Highly Pathogenic Avian Influenza (HPAI) A/H5N1 has reportedly caused outbreaks in poultry and/or wild birds in 62 countries, of which 24 were in Europe. Interestingly, out of the many genetic clades circulating in Asia, [...] Read more.

Since its emergence in South East Asia in 2003, Highly Pathogenic Avian Influenza (HPAI) A/H5N1 has reportedly caused outbreaks in poultry and/or wild birds in 62 countries, of which 24 were in Europe. Interestingly, out of the many genetic clades circulating in Asia, the westward spread of HPAI A/H5N1 to Central Asia, the Middle East, Europe and Africa was dominated by one single clade, namely clade 2.2. In this paper, we review and update through phylogenetic and gene migrational analysis the information concerning the evolution and the molecular epidemiology of HPAI A/H5N1 on the European continent. Full article

(This article belongs to the Special Issue Influenza: Pandemics and Vaccinations)

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Open AccessReview

Satellite RNAs and Satellite Viruses of Plants

by Chung-Chi Hu, Yau-Heiu Hsu and Na-Sheng Lin

Viruses 2009, 1(3), 1325-1350; https://doi.org/10.3390/v1031325 - 18 Dec 2009

Cited by 85 | Viewed by 24667

Abstract

The view that satellite RNAs (satRNAs) and satellite viruses are purely molecular parasites of their cognate helper viruses has changed. The molecular mechanisms underlying the synergistic and/or antagonistic interactions among satRNAs/satellite viruses, helper viruses, and host plants are beginning to be comprehended. This [...] Read more.

The view that satellite RNAs (satRNAs) and satellite viruses are purely molecular parasites of their cognate helper viruses has changed. The molecular mechanisms underlying the synergistic and/or antagonistic interactions among satRNAs/satellite viruses, helper viruses, and host plants are beginning to be comprehended. This review aims to summarize the recent achievements in basic and practical research, with special emphasis on the involvement of RNA silencing mechanisms in the pathogenicity, population dynamics, and, possibly, the origin(s) of these subviral agents. With further research following current trends, the comprehensive understanding of satRNAs and satellite viruses could lead to new insights into the trilateral interactions among host plants, viruses, and satellites. Full article

(This article belongs to the Special Issue Subviral RNAs)

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Open AccessReview

Viral Hybrid Vectors for Somatic Integration - Are They the Better Solution?

by Nadine Müther, Nadja Noske and Anja Ehrhardt

Viruses 2009, 1(3), 1295-1324; https://doi.org/10.3390/v1031295 - 15 Dec 2009

Cited by 15 | Viewed by 17684

Abstract

The turbulent history of clinical trials in viral gene therapy has taught us important lessons about vector design and safety issues. Much effort was spent on analyzing genotoxicity after somatic integration of therapeutic DNA into the host genome. Based on these findings major [...] Read more.

The turbulent history of clinical trials in viral gene therapy has taught us important lessons about vector design and safety issues. Much effort was spent on analyzing genotoxicity after somatic integration of therapeutic DNA into the host genome. Based on these findings major improvements in vector design including the development of viral hybrid vectors for somatic integration have been achieved. This review provides a state-of-the-art overview of available hybrid vectors utilizing viruses for high transduction efficiencies in concert with various integration machineries for random and targeted integration patterns. It discusses advantages but also limitations of each vector system. Full article

(This article belongs to the Special Issue Novel Viral Vector Systems for Gene Therapy)

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Open AccessReview

Antibody-Mediated Fcγ Receptor-Based Mechanisms of HIV Inhibition: Recent Findings and New Vaccination Strategies

by Vincent Holl, Maryse Peressin and Christiane Moog

Viruses 2009, 1(3), 1265-1294; https://doi.org/10.3390/v1031265 - 15 Dec 2009

Cited by 21 | Viewed by 11609

Abstract

The HIV/AIDS pandemic is one of the most devastating pandemics worldwide. Today, the major route of infection by HIV is sexual transmission. One of the most promising strategies for vaccination against HIV sexual infection is the development of a mucosal vaccine, which should [...] Read more.

The HIV/AIDS pandemic is one of the most devastating pandemics worldwide. Today, the major route of infection by HIV is sexual transmission. One of the most promising strategies for vaccination against HIV sexual infection is the development of a mucosal vaccine, which should be able to induce strong local and systemic protective immunity. It is believed that both humoral and cellular immune responses are needed for inducing a sterilizing protection against HIV. Recently, passive administration of monoclonal neutralizing antibodies in macaques infected by vaginal challenge demonstrated a crucial role of FcγRs in the protection afforded by these antibodies. This questioned about the role of innate and adaptive immune functions, including ADCC, ADCVI, phagocytosis of opsonized HIV particles and the production of inflammatory cytokines and chemokines, in the mechanism of HIV inhibition in vivo. Other monoclonal antibodies - non-neutralizing inhibitory antibodies - which recognize immunogenic epitopes, have been shown to display potent FcγRs-dependent inhibition of HIV replication in vitro. The potential role of these antibodies in protection against sexual transmission of HIV and their biological relevance for the development of an HIV vaccine therefore need to be determined. This review highlights the potential role of FcγRsmediated innate and adaptive immune functions in the mechanism of HIV protection. Full article

(This article belongs to the Special Issue AIDS Vaccine)

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Open AccessReview

Interplay between Herpesvirus Infection and Host Defense by PML Nuclear Bodies

by Nina Tavalai and Thomas Stamminger

Viruses 2009, 1(3), 1240-1264; https://doi.org/10.3390/v1031240 - 15 Dec 2009

Cited by 70 | Viewed by 15068

Abstract

In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication [...] Read more.

In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication at different stages. The antiviral function of ND10, however, is antagonized by viral regulatory proteins (e.g., ICP0 of herpes simplex virus; IE1 of human cytomegalovirus) which induce either a modification or disruption of ND10. This review will summarize the current knowledge on how viral replication is inhibited by ND10 proteins. Furthermore, herpesviral strategies to defeat this host defense mechanism are discussed. Full article

(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

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Open AccessReview

Current and Novel Inhibitors of HIV Protease

by Jana Pokorná, Ladislav Machala, Pavlína Řezáčová and Jan Konvalinka

Viruses 2009, 1(3), 1209-1239; https://doi.org/10.3390/v1031209 - 11 Dec 2009

Cited by 96 | Viewed by 22994

Abstract

The design, development and clinical success of HIV protease inhibitors represent one of the most remarkable achievements of molecular medicine. This review describes all nine currently available FDA-approved protease inhibitors, discusses their pharmacokinetic properties, off-target activities, side-effects, and resistance profiles. The compounds in [...] Read more.

The design, development and clinical success of HIV protease inhibitors represent one of the most remarkable achievements of molecular medicine. This review describes all nine currently available FDA-approved protease inhibitors, discusses their pharmacokinetic properties, off-target activities, side-effects, and resistance profiles. The compounds in the various stages of clinical development are also introduced, as well as alternative approaches, aiming at other functional domains of HIV PR. The potential of these novel compounds to open new way to the rational drug design of human viruses is critically assessed. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

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Open AccessArticle

A Novel Duplex Real-Time Reverse-Transcription PCR Assay for the Detection of Influenza A and the Novel Influenza A(H1N1) Strain

by Rebecca J. Rockett, Seweryn Bialasiewicz, David M. Whiley, Cheryl Bletchly, Cassandra E. Faux, Stephen B. Lambert, Graeme R. Nimmo, Michael D. Nissen and Theo P. Sloots

Viruses 2009, 1(3), 1204-1208; https://doi.org/10.3390/v1031204 - 9 Dec 2009

Cited by 3 | Viewed by 11619

Abstract

Timely implementation of antiviral treatment and other public health based responses are dependent on accurate and rapid diagnosis of the novel pandemic influenza A(H1N1) strain. In this study we developed a duplex real-time PCR (RT-PCR) (dFLU-TM) assay for the simultaneous detection of a [...] Read more.

Timely implementation of antiviral treatment and other public health based responses are dependent on accurate and rapid diagnosis of the novel pandemic influenza A(H1N1) strain. In this study we developed a duplex real-time PCR (RT-PCR) (dFLU-TM) assay for the simultaneous detection of a broad range of influenza A subtypes and specific detection of the novel H1N1 2009 pandemic strain. The assay was compared to the combined results of two previously described monoplex RT-PCR assays using 183 clinical samples and 10 seasonal influenza A isolates. Overall, the results showed that the dFLU-TM RT-PCR method is suitable for detection of influenza A, including the novel H1N1 pandemic strain, in clinical samples. Full article

(This article belongs to the Special Issue Newly Identified Respiratory Viruses)

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Open AccessReview

Henipaviruses Employ a Multifaceted Approach to Evade the Antiviral Interferon Response

by Megan L. Shaw

Viruses 2009, 1(3), 1190-1203; https://doi.org/10.3390/v1031190 - 8 Dec 2009

Cited by 21 | Viewed by 13653

Abstract

Hendra and Nipah virus, which constitute the genus Henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. Similar to other paramyxoviruses, their ability to evade the [...] Read more.

Hendra and Nipah virus, which constitute the genus Henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. Similar to other paramyxoviruses, their ability to evade the host interferon (IFN) response is conferred by the P gene. The henipavirus P gene encodes four proteins; the P, V, W and C proteins, which have all been described to inhibit the antiviral response. Further studies have revealed that these proteins have overlapping but unique properties which enable the virus to block multiple signaling pathways in the IFN response. The best characterized of these is the JAK-STAT signaling pathway which is targeted by the P, V and W proteins via an interaction with the transcription factor STAT1. In addition the V and W proteins can both limit virus-induced induction of IFN but they appear to do this via distinct mechanisms that rely on unique sequences in their C-terminal domains. The ability to generate recombinant Nipah viruses now gives us the opportunity to determine the precise role for each of these proteins and address their contribution to pathogenicity. Additionally, the question of whether these multiple anti-IFN strategies are all active in the different mammalian hosts for henipaviruses, particularly the fruit bat reservoir, warrants further exploration. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

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Open AccessCommunication

All Known Human Rhinovirus Species Are Present in Sputum Specimens of Military Recruits During Respiratory Infection

by Carita Savolainen-Kopra, Soile Blomqvist, Svetlana Kaijalainen, Ulla Jounio, Raija Juvonen, Ari Peitso, Annika Saukkoriipi, Olli Vainio, Tapani Hovi and Merja Roivainen

Viruses 2009, 1(3), 1178-1189; https://doi.org/10.3390/v1031178 - 4 Dec 2009

Cited by 24 | Viewed by 13882

Abstract

Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different [...] Read more.

Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004-2005). The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8%) specimens were HRV-positive and 36 (9.3%) HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%), belonged to HRV-A, while HRV-B strains constituted five (17.2%) of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens. Full article

(This article belongs to the Special Issue Newly Identified Respiratory Viruses)

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Open AccessArticle

Complete Nucleotide Analysis of the Structural Genome of the Infectious Bronchitis Virus Strain Md27 Reveals its Mosaic Nature

by Arun Ammayappan and Vikram N. Vakharia

Viruses 2009, 1(3), 1166-1177; https://doi.org/10.3390/v1031166 - 4 Dec 2009

Cited by 8 | Viewed by 11784

Abstract

Infectious bronchitis virus (IBV) causes highly contagious respiratory or urogenital tract diseases in chickens. The Maryland 27(Md27) strain was first isolated in 1976 from diseased chicken flocks in the Delmarva Peninsula region. To understand the genetic diversity and phylogenetic relationship of existing strains [...] Read more.

Infectious bronchitis virus (IBV) causes highly contagious respiratory or urogenital tract diseases in chickens. The Maryland 27(Md27) strain was first isolated in 1976 from diseased chicken flocks in the Delmarva Peninsula region. To understand the genetic diversity and phylogenetic relationship of existing strains with Md27, the complete nucleotide sequence of the 3’end coding region (~7.2 kb) of Md27 was determined and compared with other IBV strains and coronaviruses. It has the same S-3-M-5-N-3’ gene order, as is the case of other IBV strains. The spike gene of Md27 exhibits 97% identity with the SE17 strain. There are deletions at the spike gene, non-coding region between M and 5 genes, and at the 3’untranslated region (UTR), which is different from Ark-like strains. Phylogenetic analysis and sequence alignments demonstrate that Md27 is a chimera containing different gene segments that are most closely related to the SE17, Conn and JMK strains. This current study provides evidence for genomic mutations and intergenic recombination that have taken place in the evolution of IBV strain Md27. Full article

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Open AccessReview

Mutation Rates and Intrinsic Fidelity of Retroviral Reverse Transcriptases

by Luis Menéndez-Arias

Viruses 2009, 1(3), 1137-1165; https://doi.org/10.3390/v1031137 - 4 Dec 2009

Cited by 88 | Viewed by 17969

Abstract

Retroviruses are RNA viruses that replicate through a DNA intermediate, in a process catalyzed by the viral reverse transcriptase (RT). Although cellular polymerases and host factors contribute to retroviral mutagenesis, the RT errors play a major role in retroviral mutation. RT mutations that [...] Read more.

Retroviruses are RNA viruses that replicate through a DNA intermediate, in a process catalyzed by the viral reverse transcriptase (RT). Although cellular polymerases and host factors contribute to retroviral mutagenesis, the RT errors play a major role in retroviral mutation. RT mutations that affect the accuracy of the viral polymerase have been identified by in vitro analysis of the fidelity of DNA synthesis, by using enzymological (gel-based) and genetic assays (e.g., M13mp2 lacZ forward mutation assays). For several amino acid substitutions, these observations have been confirmed in cell culture using viral vectors. This review provides an update on studies leading to the identification of the major components of the fidelity center in retroviral RTs. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

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Graphical abstract

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Open AccessReview

HIV-1 Protease: Structural Perspectives on Drug Resistance

by Irene T. Weber and Johnson Agniswamy

Viruses 2009, 1(3), 1110-1136; https://doi.org/10.3390/v1031110 - 3 Dec 2009

Cited by 120 | Viewed by 12054

Abstract

Antiviral inhibitors of HIV-1 protease are a notable success of structure-based drug design and have dramatically improved AIDS therapy. Analysis of the structures and activities of drug resistant protease variants has revealed novel molecular mechanisms of drug resistance and guided the design of [...] Read more.

Antiviral inhibitors of HIV-1 protease are a notable success of structure-based drug design and have dramatically improved AIDS therapy. Analysis of the structures and activities of drug resistant protease variants has revealed novel molecular mechanisms of drug resistance and guided the design of tight-binding inhibitors for resistant variants. The plethora of structures reveals distinct molecular mechanisms associated with resistance: mutations that alter the protease interactions with inhibitors or substrates; mutations that alter dimer stability; and distal mutations that transmit changes to the active site. These insights will inform the continuing design of novel antiviral inhibitors targeting resistant strains of HIV. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

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Open AccessReview

Pandemic Influenza Vaccines – The Challenges

by Lars R. Haaheim, Abdullah S. Madhun and Rebecca Cox

Viruses 2009, 1(3), 1089-1109; https://doi.org/10.3390/v1031089 - 3 Dec 2009

Cited by 16 | Viewed by 11880

Abstract

Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the [...] Read more.

Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues. Full article

(This article belongs to the Special Issue Influenza: Pandemics and Vaccinations)

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Open AccessReview

HCV Innate Immune Responses

by Markus H. Heim

Viruses 2009, 1(3), 1073-1088; https://doi.org/10.3390/v1031073 - 30 Nov 2009

Cited by 5 | Viewed by 12847

Abstract

Hepatitis C virus (HCV) establishes a persistent infection in more than 70% of infected individuals. This striking ability to evade the powerful innate immune system results from viral interference occurring at several levels of the interferon (IFN) system. There is strong evidence from [...] Read more.

Hepatitis C virus (HCV) establishes a persistent infection in more than 70% of infected individuals. This striking ability to evade the powerful innate immune system results from viral interference occurring at several levels of the interferon (IFN) system. There is strong evidence from cell culture experiments that HCV can inhibit the induction of IFNβ by cleaving important proteins in the virus sensory pathways of cells such as MAVS and TRIF. There is also evidence that HCV interferes with IFNα signaling through the Jak-STAT pathway, and that HCV proteins target IFN effector systems such as protein kinase R (PKR). These in vitro findings will have to be confirmed in clinical trials investigating the molecular mechanisms of HCV interference with the innate immune system in liver samples. Full article

(This article belongs to the Special Issue Hepatitis Viruses)

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Open AccessReview

A Closer Look at the NS1 of Influenza Virus

by William G. Dundon and Ilaria Capua

Viruses 2009, 1(3), 1057-1072; https://doi.org/10.3390/v1031057 - 26 Nov 2009

Cited by 36 | Viewed by 12715

Abstract

The Non-Structural 1 (NS1) protein is a multifactorial protein of type A influenza viruses that plays an important role in the virulence of the virus. A large amount of what we know about this protein has been obtained from studies using human influenza [...] Read more.

The Non-Structural 1 (NS1) protein is a multifactorial protein of type A influenza viruses that plays an important role in the virulence of the virus. A large amount of what we know about this protein has been obtained from studies using human influenza isolates and, consequently, the human NS1 protein. The current global interest in avian influenza, however, has highlighted a number of sequence and functional differences between the human and avian NS1. This review discusses these differences in addition to describing potential uses of NS1 in the management and control of avian influenza outbreaks. Full article

(This article belongs to the Special Issue Influenza: Pandemics and Vaccinations)

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Open AccessReview

Rotavirus Antagonism of the Innate Immune Response

by Michelle M. Arnold and John T. Patton

Viruses 2009, 1(3), 1035-1056; https://doi.org/10.3390/v1031035 - 24 Nov 2009

Cited by 19 | Viewed by 17294

Abstract

Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN)-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus [...] Read more.

Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN)-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus encodes a nonstructural protein (NSP1) that induces the degradation of proteins involved in regulating IFN expression, such as members of the IFN regulatory factor (IRF) family. In some instances, NSP1 also subverts IFN expression by causing the degradation of a component of the E3 ubiquitin ligase complex responsible for activating NF-κB. By antagonizing multiple components of the IFN-induction pathway, NSP1 aids viral spread and contributes to rotavirus pathogenesis. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

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Open AccessReview

Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

by Artur Summerfield and Kenneth C. McCullough

Viruses 2009, 1(3), 1022-1034; https://doi.org/10.3390/v1031022 - 24 Nov 2009

Cited by 24 | Viewed by 11996

Abstract

Dendritic cells (DC) are major players in both innate and adaptive immune responses against influenza virus. These immune responses, as well as the important interface between the innate and adaptive systems, are orchestrated by specialized subsets of DC, including conventional steady-state DC, migratory [...] Read more.

Dendritic cells (DC) are major players in both innate and adaptive immune responses against influenza virus. These immune responses, as well as the important interface between the innate and adaptive systems, are orchestrated by specialized subsets of DC, including conventional steady-state DC, migratory DC and plasmacytoid DC. The characteristics and efficacy of the responses are dependent on the relative activity of these DC subsets, rendering DC crucial for the development of both naïve and memory immune responses. However, due to their critical role, DC also contribute to the immunopathological processes observed during acute influenza, such as that caused by the pathogenic H5N1 viruses. Therein, the role of different DC subsets in the induction of interferon type I, proinflammatory cytokine and chemokine responses is important for the outcome of interaction between the virus and host immune defences. The present review will present current knowledge on this area, relating to the importance of DC activity for the induction of efficacious humoral and cell-mediated immune responses. This will include the main viral elements associated with the triggering or inhibition of DC activation. Finally, the current knowledge on understanding how differences in various vaccines influence the manner of immune defence induction will be presented. Full article

(This article belongs to the Special Issue Influenza: Pandemics and Vaccinations)

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Open AccessReview

Bunyaviruses and the Type I Interferon System

by Richard M. Elliott and Friedemann Weber

Viruses 2009, 1(3), 1003-1021; https://doi.org/10.3390/v1031003 - 23 Nov 2009

Cited by 53 | Viewed by 13899

Abstract

The family Bunyaviridae contains more than 350 viruses that are distributed throughout the world. Most members of the family are transmitted by arthopods, and several cause disease in man, domesticated animals and crop plants. Despite being recognized as an emerging threat, details of [...] Read more.

The family Bunyaviridae contains more than 350 viruses that are distributed throughout the world. Most members of the family are transmitted by arthopods, and several cause disease in man, domesticated animals and crop plants. Despite being recognized as an emerging threat, details of the virulence mechanisms employed by bunyaviruses are scant. In this article we summarise the information currently available on how these viruses are able to establish infection when confronted with a powerful antiviral interferon system. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

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Open AccessReview

Innate and Adaptive Immune Responses to Herpes Simplex Virus

by Tracy Chew, Kathryne E. Taylor and Karen L. Mossman

Viruses 2009, 1(3), 979-1002; https://doi.org/10.3390/v1030979 - 18 Nov 2009

Cited by 107 | Viewed by 18452

Abstract

Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized in [...] Read more.

Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized in vitro and in vivo. Cell types such as NK cells and pDCs contribute to innate anti-HSV responses in vivo. Finally, the adaptive response includes both humoral and cellular components that play important roles in antiviral control and latency. This review summarizes the innate and adaptive effectors that contribute to susceptibility, immune control and pathogenesis of HSV, and highlights the delicate interplay between these two important arms of immunity. Full article

(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

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Open AccessReview

Cellular Players in the Herpes Simplex Virus Dependent Apoptosis Balancing Act

by Marie L. Nguyen and John A. Blaho

Viruses 2009, 1(3), 965-978; https://doi.org/10.3390/v1030965 - 18 Nov 2009

Cited by 14 | Viewed by 14174

Abstract

Apoptosis is triggered as an intrinsic defense against numerous viral infections. Almost every virus encodes apoptotic modulators, and the herpes simplex viruses (HSV) are no exception. During HSV infection, there is an intricate balance between pro- and anti-apoptotic factors that delays apoptotic death [...] Read more.

Apoptosis is triggered as an intrinsic defense against numerous viral infections. Almost every virus encodes apoptotic modulators, and the herpes simplex viruses (HSV) are no exception. During HSV infection, there is an intricate balance between pro- and anti-apoptotic factors that delays apoptotic death until the virus has replicated. Perturbations in the apoptotic balance can cause premature cell death and have the potential to dramatically alter the outcome of infection. Recently, certain cellular genes have been shown to regulate sensitivity to HSV-dependent apoptosis. This review summarizes current knowledge of the cellular genes that impact the apoptotic balance during HSV infection. Full article

(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

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Open AccessReview

Therapeutic Approaches Using Host Defence Peptides to Tackle Herpes Virus Infections

by Håvard Jenssen

Viruses 2009, 1(3), 939-964; https://doi.org/10.3390/v1030939 - 18 Nov 2009

Cited by 26 | Viewed by 13858

Abstract

One of the most common viral infections in humans is caused by herpes simplex virus (HSV). It can easily be treated with nucleoside analogues (e.g., acyclovir), but resistant strains are on the rise. Naturally occurring antimicrobial peptides have been demonstrated to possess antiviral [...] Read more.

One of the most common viral infections in humans is caused by herpes simplex virus (HSV). It can easily be treated with nucleoside analogues (e.g., acyclovir), but resistant strains are on the rise. Naturally occurring antimicrobial peptides have been demonstrated to possess antiviral activity against HSV. New evidence has also indicated that these host defence peptides are able to selectively stimulate the innate immune system to fight of infections. This review will focus on the anti-HSV activity of such peptides (both natural and synthetic), describe their mode of action and their clinical potential. Full article

(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

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Open AccessArticle

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines

by Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry and Michael A. Barry

Viruses 2009, 1(3), 920-938; https://doi.org/10.3390/v1030920 - 10 Nov 2009

Cited by 29 | Viewed by 12358

Abstract

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. [...] Read more.

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5-immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in the HD-Ad5 group. In this study, neutralizing antibody and T cell responses were compared between the groups before and after rectal challenge with CCR5-tropic SHIV-SF162P3. When serum samples were assayed for neutralizing antibodies, only weak activity was observed. T cell responses against env epitopes were higher in the serotype-switched group. When these animals were challenged rectally with SHIV-SF162P3, both the Ad5 and serotype-switch groups significantly reduced peak viral loads 2 to 10-fold 2 weeks after infection. Peak viral loads were significantly lower for the serotype-switched group as compared to the HD-Ad5-immunized group. Viral loads declined over 18 weeks after infection with some animals viremia reducing nearly 4 logs from the peak. These data demonstrate significant mucosal vaccine effects after immunization with only env antigens. These data also demonstrate HD-Ad vectors are a robust platform for vaccination. Full article

(This article belongs to the Special Issue AIDS Vaccine)

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Open AccessReview

Defective Interfering RNAs: Foes of Viruses and Friends of Virologists

by Kunj B. Pathak and Peter D. Nagy

Viruses 2009, 1(3), 895-919; https://doi.org/10.3390/v1030895 - 10 Nov 2009

Cited by 85 | Viewed by 19168

Abstract

Defective interfering (DI) RNAs are subviral RNAs produced during multiplication of RNA viruses by the error-prone viral replicase. DI-RNAs are parasitic RNAs that are derived from and associated with the parent virus, taking advantage of viral-coded protein factors for their multiplication. Recent advances [...] Read more.

Defective interfering (DI) RNAs are subviral RNAs produced during multiplication of RNA viruses by the error-prone viral replicase. DI-RNAs are parasitic RNAs that are derived from and associated with the parent virus, taking advantage of viral-coded protein factors for their multiplication. Recent advances in the field of DI RNA biology has led to a greater understanding about generation and evolution of DI-RNAs as well as the mechanism of symptom attenuation. Moreover, DI-RNAs are versatile tools in the hands of virologists and are used as less complex surrogate templates to understand the biology of their helper viruses. The ease of their genetic manipulation has resulted in rapid discoveries on cis-acting RNA replication elements required for replication and recombination. DI-RNAs have been further exploited to discover host factors that modulate Tomato bushy stunt virus replication, as well as viral RNA recombination. This review discusses the current models on generation and evolution of DI-RNAs, the roles of viral and host factors in DI-RNA replication, and the mechanisms of disease attenuation. Full article

(This article belongs to the Special Issue Subviral RNAs)

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Open AccessReview

Reverse Transcriptase and Cellular Factors: Regulators of HIV-1 Reverse Transcription

by Kylie Warren, David Warrilow, Luke Meredith and David Harrich

Viruses 2009, 1(3), 873-894; https://doi.org/10.3390/v1030873 - 10 Nov 2009

Cited by 38 | Viewed by 16659

Abstract

There is ample evidence that synthesis of HIV-1 proviral DNA from the viral RNA genome during reverse transcription requires host factors. However, only a few cellular proteins have been described in detail that affect reverse transcription and interact with reverse transcriptase (RT). HIV-1 [...] Read more.

There is ample evidence that synthesis of HIV-1 proviral DNA from the viral RNA genome during reverse transcription requires host factors. However, only a few cellular proteins have been described in detail that affect reverse transcription and interact with reverse transcriptase (RT). HIV-1 integrase is an RT binding protein and a number of IN-binding proteins including INI1, components of the Sin3a complex, and Gemin2 affect reverse transcription. In addition, recent studies implicate the cellular proteins HuR, AKAP149, and DNA topoisomerase I in reverse transcription through an interaction with RT. In this review we will consider interactions of reverse transcription complex with viral and cellular factors and how they affect the reverse transcription process. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

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Open AccessReview

Molecular Mechanisms Underlying Hepatocellular Carcinoma

by Philippe Merle and Christian Trepo

Viruses 2009, 1(3), 852-872; https://doi.org/10.3390/v1030852 - 9 Nov 2009

Cited by 34 | Viewed by 13442

Abstract

Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem [...] Read more.

Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21^Cip1and p16^INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis. Full article

(This article belongs to the Special Issue Hepatitis Viruses)

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Interferon Response and Viral Evasion by Members of the Family Rhabdoviridae

by Elizabeth J. Faul, Douglas S. Lyles and Matthias J. Schnell

Viruses 2009, 1(3), 832-851; https://doi.org/10.3390/v1030832 - 9 Nov 2009

Cited by 41 | Viewed by 13577

Abstract

Like many animal viruses, those of the Rhabdoviridae family, are able to antagonize the type I interferon response and cause disease in mammalian hosts. Though these negative-stranded RNA viruses are very simple and code for as few as five proteins, they have been [...] Read more.

Like many animal viruses, those of the Rhabdoviridae family, are able to antagonize the type I interferon response and cause disease in mammalian hosts. Though these negative-stranded RNA viruses are very simple and code for as few as five proteins, they have been seen to completely abrogate the type I interferon response early in infection. In this review, we will discuss the viral organization and type I interferon evasion of rhabdoviruses, focusing on vesicular stomatitis virus (VSV) and rabies virus (RABV). Despite their structural similarities, VSV and RABV have completely different mechanisms by which they avert the host immune response. VSV relies on the matrix protein to interfere with host gene transcription and nuclear export of anti-viral mRNAs. Alternatively, RABV uses its phosphoprotein to interfere with IRF-3 phosphorylation and STAT1 signaling. Understanding the virus-cell interactions and viral proteins necessary to evade the immune response is important in developing effective vaccines and therapeutics for this viral family. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

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Open AccessReview

Hepatitis Delta Virus RNA Replication

by Chung-Hsin Tseng and Michael M. C. Lai

Viruses 2009, 1(3), 818-831; https://doi.org/10.3390/v1030818 - 6 Nov 2009

Cited by 46 | Viewed by 15939

Abstract

Hepatitis delta virus (HDV) is a distant relative of plant viroids in the animal world. Similar to plant viroids, HDV replicates its circular RNA genome using a double rolling-circle mechanism. Nevertheless, the production of hepatitis delta antigen (HDAg), which is indispensible for HDV [...] Read more.

Hepatitis delta virus (HDV) is a distant relative of plant viroids in the animal world. Similar to plant viroids, HDV replicates its circular RNA genome using a double rolling-circle mechanism. Nevertheless, the production of hepatitis delta antigen (HDAg), which is indispensible for HDV replication, is a unique feature distinct from plant viroids, which do not encode any protein. Here the HDV RNA replication cycle is reviewed, with emphasis on the function of HDAg in modulating RNA replication and the nature of the enzyme involved. Full article

(This article belongs to the Special Issue Subviral RNAs)

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Open AccessArticle

Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

by Xiaodong Xiao, Weizao Chen, Yang Feng and Dimiter S. Dimitrov

Viruses 2009, 1(3), 802-817; https://doi.org/10.3390/v1030802 - 6 Nov 2009

Cited by 55 | Viewed by 13686

Abstract

Several human monoclonal antibodies (hmAbs) and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on [...] Read more.

Several human monoclonal antibodies (hmAbs) and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env) to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG) lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM) affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i) antibodies in HIV-1-infected patients (X5 is a CD4i antibody) as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and intermediate antibodies that together with Envs could be used as a conceptually novel type of candidate vaccines. Such candidate vaccines based on two or more immunogens could help guiding the immune system through complex maturation pathways for elicitation of antibodies that are similar or identical to antibodies with known properties. Full article

(This article belongs to the Special Issue AIDS Vaccine)

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The Interaction Between Lentiviral Integrase and LEDGF: Structural and Functional Insights

by Stephen Hare and Peter Cherepanov

Viruses 2009, 1(3), 780-801; https://doi.org/10.3390/v1030780 - 6 Nov 2009

Cited by 20 | Viewed by 16174

Abstract

Since its initial description as an HIV-1 integrase (IN) interactor seven years ago, LEDGF has become one of the best-characterized host factors involved in viral replication. Results of intensive studies in several laboratories indicated that the protein serves as a targeting factor for [...] Read more.

Since its initial description as an HIV-1 integrase (IN) interactor seven years ago, LEDGF has become one of the best-characterized host factors involved in viral replication. Results of intensive studies in several laboratories indicated that the protein serves as a targeting factor for the lentiviral DNA integration machinery, and accounts for the characteristic preference of Lentivirus to integrate within active transcription units. The IN-LEDGF interaction has been put forward as a promising target for antiretroviral drug development and as a potential tool to improve safety of lentiviral vectors for use in gene therapy. Additionally, as a natural ligand of lentiviral IN proteins, LEDGF has been successfully used in structural biology studies of retroviral DNA integration. This review focuses on the structural aspects of the IN-LEDGF interaction and their functional consequences. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

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The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

by Christina Paulus and Michael Nevels

Viruses 2009, 1(3), 760-779; https://doi.org/10.3390/v1030760 - 5 Nov 2009

Cited by 52 | Viewed by 16584

Abstract

The major immediate-early (IE) gene of human cytomegalovirus (CMV) is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the [...] Read more.

The major immediate-early (IE) gene of human cytomegalovirus (CMV) is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses. Full article

(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

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Viruses, Volume 1, Issue 3 (December 2009) – 49 articles , Pages 335-1363

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