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Viruses, Volume 3, Issue 4 (April 2011), Pages 278-422

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Research

Jump to: Review, Other

Open AccessArticle Efficient Sensing of Avian Influenza Viruses by Porcine Plasmacytoid Dendritic Cells
Viruses 2011, 3(4), 312-330; doi:10.3390/v3040312
Received: 28 February 2011 / Revised: 15 March 2011 / Accepted: 17 March 2011 / Published: 30 March 2011
Cited by 9 | PDF Full-text (661 KB)
Abstract
H5N1 influenza A virus (IAV) infections in human remain rare events but have been associated with severe disease and a higher mortality rate compared to infections with seasonal strains. An excessive release of pro-inflammatory cytokine together with a greater virus dissemination potential [...] Read more.
H5N1 influenza A virus (IAV) infections in human remain rare events but have been associated with severe disease and a higher mortality rate compared to infections with seasonal strains. An excessive release of pro-inflammatory cytokine together with a greater virus dissemination potential have been proposed to explain the high virulence observed in human and other mammalian and avian species. Among the cells involved in the cytokine storm, plasmacytoid dendritic cells (pDC) could play an important role considering their unique capacity to secrete massive amounts of type I interferon (IFN). Considering the role of IFN as a major component of antiviral responses as well as in priming inflammatory responses, we aimed to characterize the induction of IFN-α release upon infection with IAV originating from various avian and mammalian species in a comparative way. In our porcine pDC model, we showed that the viral components triggering IFN responses related to the ability to hemagglutinate, although virosomes devoid of viral RNA were non-stimulatory. Heat-treatment at 65 °C but not chemical inactivation destroyed the ability of IAV to stimulate pDC. All IAV tested induced IFN-α but at different levels and showed different dose-dependencies. H5 and H7 subtypes, in particular H5N1, stimulated pDC at lower doses when compared to mammalian IAV. At high viral doses, IFN-α levels reached by some mammalian IAV surpassed those induced by avian isolates. Although sialic acid-dependent entry was demonstrated, the α-2,3 or α-2,6 binding specificity alone did not explain the differences observed. Furthermore, we were unable to identify a clear role of the hemagglutinin, as the IFN-a doses-response profiles did not clearly differ when viruses with all genes of identical avian origin but different HA were compared. This was found with IAV bearing an HA derived from either a low, a high pathogenic H5N1, or a human H3. Stimulation of pDC was associated with pDC depletion within the cultures. Taken together and considering the efficient sensing of H5N1 at low dose, pDC on one side may play a role in the cytokine storm observed during severe disease, on the other hand could participate in early antiviral responses limiting virus replication. Full article

Review

Jump to: Research, Other

Open AccessReview Actin’ up: Herpesvirus Interactions with Rho GTPase Signaling
Viruses 2011, 3(4), 278-292; doi:10.3390/v3040278
Received: 31 January 2011 / Revised: 15 March 2011 / Accepted: 16 March 2011 / Published: 24 March 2011
Cited by 7 | PDF Full-text (321 KB)
Abstract
Herpesviruses constitute a very large and diverse family of DNA viruses, which can generally be subdivided in alpha-, beta- and gammaherpesvirus subfamilies. Increasing evidence indicates that many herpesviruses interact with cytoskeleton-regulating Rho GTPase signaling pathways during different phases of their replication cycle. [...] Read more.
Herpesviruses constitute a very large and diverse family of DNA viruses, which can generally be subdivided in alpha-, beta- and gammaherpesvirus subfamilies. Increasing evidence indicates that many herpesviruses interact with cytoskeleton-regulating Rho GTPase signaling pathways during different phases of their replication cycle. Because of the large differences between herpesvirus subfamilies, the molecular mechanisms and specific consequences of individual herpesvirus interactions with Rho GTPase signaling may differ. However, some evolutionary distinct but similar general effects on Rho GTPase signaling and the cytoskeleton have also been reported. Examples of these include Rho GTPase-mediated nuclear translocation of virus during entry in a host cell and Rho GTPase-mediated viral cell-to-cell spread during later stages of infection. The current review gives an overview of both general and individual interactions of herpesviruses with Rho GTPase signaling. Full article
(This article belongs to the Special Issue Cytoskeleton in Viral Infections)
Open AccessReview How HIV Takes Advantage of the Cytoskeleton in Entry and Replication
Viruses 2011, 3(4), 293-311; doi:10.3390/v3040293
Received: 2 February 2011 / Revised: 11 March 2011 / Accepted: 19 March 2011 / Published: 28 March 2011
Cited by 26 | PDF Full-text (474 KB)
Abstract
The host cell cytoskeleton plays a key role in the life cycle of viral pathogens whose propagation depends on mandatory intracellular steps. Accordingly, also the human immunodeficiency virus type 1 (HIV-1) has evolved strategies to exploit and modulate in particular the actin [...] Read more.
The host cell cytoskeleton plays a key role in the life cycle of viral pathogens whose propagation depends on mandatory intracellular steps. Accordingly, also the human immunodeficiency virus type 1 (HIV-1) has evolved strategies to exploit and modulate in particular the actin cytoskeleton for its purposes. This review will recapitulate recent findings on how HIV-1 hijacks the cytoskeleton to facilitate entry into, transport within and egress from host cells as well as to commandeer communication of infected with uninfected bystander cells. Full article
(This article belongs to the Special Issue Cytoskeleton in Viral Infections)
Open AccessReview Actin in Herpesvirus Infection
Viruses 2011, 3(4), 336-346; doi:10.3390/v3040336
Received: 9 February 2011 / Revised: 24 March 2011 / Accepted: 28 March 2011 / Published: 12 April 2011
Cited by 21 | PDF Full-text (242 KB)
Abstract
Actin is important for a variety of cellular processes, including uptake of extracellular material and intracellular transport. Several emerging lines of evidence indicate that herpesviruses exploit actin and actin-associated myosin motors for viral entry, intranuclear transport of capsids, and virion egress. The goal [...] Read more.
Actin is important for a variety of cellular processes, including uptake of extracellular material and intracellular transport. Several emerging lines of evidence indicate that herpesviruses exploit actin and actin-associated myosin motors for viral entry, intranuclear transport of capsids, and virion egress. The goal of this review is to explore these processes and to highlight potential future directions for this area of research. Full article
(This article belongs to the Special Issue Cytoskeleton in Viral Infections)
Figures

Open AccessReview Clinical Management of HIV Drug Resistance
Viruses 2011, 3(4), 347-378; doi:10.3390/v3040347
Received: 9 March 2011 / Accepted: 30 March 2011 / Published: 14 April 2011
Cited by 27 | PDF Full-text (687 KB)
Abstract
Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. [...] Read more.
Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. Full article
(This article belongs to the Special Issue HIV Drug Resistance 2010)
Open AccessReview An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses
Viruses 2011, 3(4), 379-397; doi:10.3390/v3040379
Received: 15 February 2011 / Revised: 2 March 2011 / Accepted: 10 March 2011 / Published: 15 April 2011
PDF Full-text (333 KB) | Supplementary Files
Abstract
The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it [...] Read more.
The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues. Full article
(This article belongs to the Special Issue Virus Dynamics and Evolution)
Open AccessReview Insertional Oncogenesis by Non-Acute Retroviruses: Implications for Gene Therapy
Viruses 2011, 3(4), 398-422; doi:10.3390/v3040398
Received: 16 March 2011 / Accepted: 31 March 2011 / Published: 15 April 2011
Cited by 16 | PDF Full-text (305 KB)
Abstract
Retroviruses cause cancers in a variety of animals and humans. Research on retroviruses has provided important insights into mechanisms of oncogenesis in humans, including the discovery of viral oncogenes and cellular proto-oncogenes. The subject of this review is the mechanisms by which [...] Read more.
Retroviruses cause cancers in a variety of animals and humans. Research on retroviruses has provided important insights into mechanisms of oncogenesis in humans, including the discovery of viral oncogenes and cellular proto-oncogenes. The subject of this review is the mechanisms by which retroviruses that do not carry oncogenes (non-acute retroviruses) cause cancers. The common theme is that these tumors result from insertional activation of cellular proto-oncogenes by integration of viral DNA. Early research on insertional activation of proto-oncogenes in virus-induced tumors is reviewed. Research on non-acute retroviruses has led to the discovery of new proto-oncogenes through searches for common insertion sites (CISs) in virus-induced tumors. Cooperation between different proto-oncogenes in development of tumors has been elucidated through the study of retrovirus-induced tumors, and retroviral infection of genetically susceptible mice (retroviral tagging) has been used to identify cellular proto-oncogenes active in specific oncogenic pathways. The pace of proto-oncogene discovery has been accelerated by technical advances including PCR cloning of viral integration sites, the availability of the mouse genome sequence, and high throughput DNA sequencing. Insertional activation has proven to be a significant risk in gene therapy trials to correct genetic defects with retroviral vectors. Studies on non-acute retroviral oncogenesis provide insight into the potential risks, and the mechanisms of oncogenesis. Full article
(This article belongs to the Special Issue Cell Transformation by RNA Viruses)

Other

Jump to: Research, Review

Open AccessCommentary Initiation of HIV Reverse Transcription: Is Enzyme Flipping Required?
Viruses 2011, 3(4), 331-335; doi:10.3390/v3040331
Received: 9 March 2011 / Revised: 1 April 2011 / Accepted: 1 April 2011 / Published: 12 April 2011
PDF Full-text (127 KB)
Abstract
Liu and colleagues have recently studied dynamic changes in the orientation of HIV reverse transcriptase (RT) on its nucleic acid substrate during initiation of DNA synthesis. The authors employed a single molecule FRET assay and revealed the existence of an equilibrium between [...] Read more.
Liu and colleagues have recently studied dynamic changes in the orientation of HIV reverse transcriptase (RT) on its nucleic acid substrate during initiation of DNA synthesis. The authors employed a single molecule FRET assay and revealed the existence of an equilibrium between polymerase-competent and “flipped” polymerase-incompetent orientations. RT flipping correlates with enzyme pausing during initiation, while the transition to the processive elongation phase correlates with increases in the population of polymerase-competent complexes. The potential biological significance of these findings is discussed in this commentary in lieu of the entire process of reverse transcription. Full article
(This article belongs to the Section Editorial)

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