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Viruses, Volume 2, Issue 8 (August 2010) – 20 articles , Pages 1504-1820

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300 KiB  
Review
Coronavirus Genomics and Bioinformatics Analysis
by Patrick C. Y. Woo, Yi Huang, Susanna K. P. Lau and Kwok-Yung Yuen
Viruses 2010, 2(8), 1804-1820; https://doi.org/10.3390/v2081803 - 24 Aug 2010
Cited by 603 | Viewed by 31469
Abstract
The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known [...] Read more.
The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999-2002, with estimated substitution rate of 4´10-4 to 2´10-2 substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses. Full article
(This article belongs to the Special Issue Viral Genomics and Bioinformatics)
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Review
Last Stop Before Exit – Hepatitis C Assembly and Release as Antiviral Drug Targets
by Birke Andrea Tews, Costin-Ioan Popescu and Jean Dubuisson
Viruses 2010, 2(8), 1782-1803; https://doi.org/10.3390/v2081782 - 24 Aug 2010
Cited by 5 | Viewed by 12499
Abstract
Chronic Hepatitis C infection is a global health problem. While primary infection is often inapparent, it becomes chronic in most cases. Chronic infection with Hepatitis C virus (HCV) frequently leads to liver cirrhosis or liver cancer. Consequently, HCV infection is one of the [...] Read more.
Chronic Hepatitis C infection is a global health problem. While primary infection is often inapparent, it becomes chronic in most cases. Chronic infection with Hepatitis C virus (HCV) frequently leads to liver cirrhosis or liver cancer. Consequently, HCV infection is one of the leading causes for liver transplantation in industrialized countries. Current treatment is not HCV specific and is only effective in about half of the infected patients. This situation underlines the need for new antivirals against HCV. To develop new and more efficient drugs, it is essential to specifically target the different steps of the viral life cycle. Of those steps, the targeting of HCV assembly has the potential to abolish virus production. This review summarizes the advances in our understanding of HCV particle assembly and the identification of new antiviral targets of potential interest in this late step of the HCV life cycle. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
Antiviral Strategies for Pandemic and Seasonal Influenza
by Maria Hedlund, Jeffrey L. Larson and Fang Fang
Viruses 2010, 2(8), 1766-1781; https://doi.org/10.3390/v2081766 - 20 Aug 2010
Cited by 12 | Viewed by 7830
Abstract
While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and [...] Read more.
While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein. Full article
(This article belongs to the Special Issue Antivirals Against Influenza)
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Review
Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel
by Laurent Chatel-Chaix, Martin Baril and Daniel Lamarre
Viruses 2010, 2(8), 1752-1765; https://doi.org/10.3390/v2081752 - 20 Aug 2010
Cited by 55 | Viewed by 15943
Abstract
Hepatitis C virus (HCV) infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a [...] Read more.
Hepatitis C virus (HCV) infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease) that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
Core as a Novel Viral Target for Hepatitis C Drugs
by Arthur Donny Strosberg, Smitha Kota, Virginia Takahashi, John K. Snyder and Guillaume Mousseau
Viruses 2010, 2(8), 1734-1751; https://doi.org/10.3390/v2081734 - 20 Aug 2010
Cited by 31 | Viewed by 13474
Abstract
Hepatitis C virus (HCV) infects over 130 million people worldwide and is a major cause of liver disease. No vaccine is available. Novel specific drugs for HCV are urgently required, since the standard-of-care treatment of pegylated interferon combined with ribavirin is poorly tolerated [...] Read more.
Hepatitis C virus (HCV) infects over 130 million people worldwide and is a major cause of liver disease. No vaccine is available. Novel specific drugs for HCV are urgently required, since the standard-of-care treatment of pegylated interferon combined with ribavirin is poorly tolerated and cures less than half of the treated patients. Promising, effective direct-acting drugs currently in the clinic have been described for three of the ten potential HCV target proteins: NS3/NS4A protease, NS5B polymerase and NS5A, a regulatory phosphoprotein. We here present core, the viral capsid protein, as another attractive, non-enzymatic target, against which a new class of anti-HCV drugs can be raised. Core plays a major role in the virion’s formation, and interacts with several cellular proteins, some of which are involved in host defense mechanisms against the virus. This most conserved of all HCV proteins requires oligomerization to function as the organizer of viral particle assembly. Using core dimerization as the basis of transfer-of-energy screening assays, peptides and small molecules were identified which not only inhibit core-core interaction, but also block viral production in cell culture. Initial chemical optimization resulted in compounds active in single digit micromolar concentrations. Core inhibitors could be used in combination with other HCV drugs in order to provide novel treatments of Hepatitis C. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
Targeting HCV Entry For Development of Therapeutics
by Flossie Wong-Staal, Andrew J. Syder and Jeffrey F. McKelvy
Viruses 2010, 2(8), 1718-1733; https://doi.org/10.3390/v2081718 - 18 Aug 2010
Cited by 25 | Viewed by 12948
Abstract
Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV) entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication [...] Read more.
Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV) entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication inhibitors now under development. The current model for the pathway of entry involves the initial docking of the virus onto the cell surface through interactions of virion envelope and associated low density lipoproteins (LDL) with cell surface glycosaminoglycans and lipoprotein receptors, followed by more specific utilization with other hepatocyte membrane proteins: Scavenger Receptor Class B type 1 (SR-BI), CD81, Claudin 1 (CLDN1) and Occludin (OCLN). The use of blockers of these interactions, e.g. specific antibodies, suggests that inhibition of any one step in the entry pathway can inhibit infection. Despite this knowledge base, the tools for compound screening, HCV pseudoparticles (HCVpp) and cell culture virus (HCVcc), and the ability to adapt them to industrial use are only recently available and as a result drug discovery initiatives are in their infancy. Several therapies aiming at modulating the virus envelope to prevent host cell binding are in early clinical testing. The first test case for blocking a cellular co-receptor is an SR-BI modulator. ITX 5061, an orally active small molecule, targets SR-BI and has shown potent antiviral activity against HCVpp and HCVcc. ITX 5061 has exhibited good safety in previous clinical studies, and is being evaluated in the clinic in chronic HCV patients and patients undergoing liver transplantation. Entry inhibitors promise to be valuable players in the future development of curative therapy against HCV. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
Dendritic Cells and HIV-1 Trans-Infection
by David McDonald
Viruses 2010, 2(8), 1704-1717; https://doi.org/10.3390/v2081704 - 17 Aug 2010
Cited by 44 | Viewed by 13989
Abstract
Dendritic cells initiate and sustain immune responses by migrating to sites of pathogenic insult, transporting antigens to lymphoid tissues and signaling immune specific activation of T cells through the formation of the immunological synapse. Dendritic cells can also transfer intact, infectious HIV-1 to [...] Read more.
Dendritic cells initiate and sustain immune responses by migrating to sites of pathogenic insult, transporting antigens to lymphoid tissues and signaling immune specific activation of T cells through the formation of the immunological synapse. Dendritic cells can also transfer intact, infectious HIV-1 to CD4 T cells through an analogous structure, the infectious synapse. This replication independent mode of HIV-1 transmission, known as trans-infection, greatly increases T cell infection in vitro and is thought to contribute to viral dissemination in vivo. This review outlines the recent data defining the mechanisms of trans-infection and provides a context for the potential contribution of trans-infection in HIV-1 disease. Full article
(This article belongs to the Special Issue Transmission of Retroviruses across Virological Synapses)
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Review
Adenoviral Producer Cells
by Imre Kovesdi and Susan J. Hedley
Viruses 2010, 2(8), 1681-1703; https://doi.org/10.3390/v2081681 - 16 Aug 2010
Cited by 72 | Viewed by 19670
Abstract
Adenovirus (Ad) vectors, in particular those of the serotype 5, are highly attractive for a wide range of gene therapy, vaccine and virotherapy applications (as discussed in further detail in this issue). Wild type Ad5 virus can replicate in numerous tissue types but [...] Read more.
Adenovirus (Ad) vectors, in particular those of the serotype 5, are highly attractive for a wide range of gene therapy, vaccine and virotherapy applications (as discussed in further detail in this issue). Wild type Ad5 virus can replicate in numerous tissue types but to use Ad vectors for therapeutic purposes the viral genome requires modification. In particular, if the viral genome is modified in such a way that the viral life cycle is interfered with, a specific producer cell line is required to provide trans-complementation to overcome the modification and allow viral production. This can occur in two ways; use of a producer cell line that contains specific adenoviral sequences incorporated into the cell genome to trans-complement, or use of a producer cell line that naturally complements for the modified Ad vector genome. This review concentrates on producer cell lines that complement non-replicating adenoviral vectors, starting with the historical HEK293 cell line developed in 1977 for first generation Ad vectors. In addition the problem of replication-competent adenovirus (RCA) contamination in viral preparations from HEK293 cells is addressed leading to the development of alternate cell lines. Furthermore novel cell lines for more complex Ad vectors and alternate serotype Ad vectors are discussed. Full article
(This article belongs to the Special Issue Adenoviral Vectors)
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Review
HIV-1 Virological Synapse: Live Imaging of Transmission
by Jerome Feldmann and Olivier Schwartz
Viruses 2010, 2(8), 1666-1680; https://doi.org/10.3390/v2081666 - 12 Aug 2010
Cited by 36 | Viewed by 7404
Abstract
A relatively new aspect of HIV-1 biology is the ability of the virus to infect cells by direct cellular contacts across a specialized structure, the virological synapse. This process was recently described through live cell imaging. Together with the accumulated knowledge on cellular [...] Read more.
A relatively new aspect of HIV-1 biology is the ability of the virus to infect cells by direct cellular contacts across a specialized structure, the virological synapse. This process was recently described through live cell imaging. Together with the accumulated knowledge on cellular and molecular structures involved in cell-to-cell transmission of HIV-1, the visualization of the virological synapse in video-microscopy has brought exciting new hypotheses on its underlying mechanisms. This review will recapitulate current knowledge with a particular emphasis on the questions live microscopy has raised. Full article
(This article belongs to the Special Issue Transmission of Retroviruses across Virological Synapses)
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Review
Possibilities for RNA Interference in Developing Hepatitis C Virus Therapeutics
by Kristi L. Berger and Glenn Randall
Viruses 2010, 2(8), 1647-1665; https://doi.org/10.3390/v2081647 - 6 Aug 2010
Cited by 6 | Viewed by 10934
Abstract
The discovery and characterization of the RNA interference (RNAi) pathway has been one of the most important scientific developments of the last 12 years. RNAi is a cellular pathway wherein small RNAs control the expression of genes by either degrading homologous RNAs or [...] Read more.
The discovery and characterization of the RNA interference (RNAi) pathway has been one of the most important scientific developments of the last 12 years. RNAi is a cellular pathway wherein small RNAs control the expression of genes by either degrading homologous RNAs or preventing the translation of RNAs with partial homology. It has impacted basic biology on two major fronts. The first is the discovery of microRNAs (miRNAs), which regulate almost every cellular process and are required for some viral infections, including hepatitis C virus (HCV). The second front is the use of small interfering RNAs (siRNAs) as the first robust tool for mammalian cellular genetics. This has led to the identification of hundreds of cellular genes that are important for HCV infection. There is now a major push to adapt RNAi technology to the clinic. In this review, we explore the impact of RNAi in understanding HCV biology, the progress in design of RNAi-based therapeutics for HCV, and remaining obstacles. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
The Hepatitis C Virus Nonstructural Protein 2 (NS2): An Up-and-Coming Antiviral Drug Target
by Ivo C. Lorenz
Viruses 2010, 2(8), 1635-1646; https://doi.org/10.3390/v2081635 - 6 Aug 2010
Cited by 18 | Viewed by 10684
Abstract
Infection with Hepatitis C Virus (HCV) continues to be a major global health problem. To overcome the limitations of current therapies using interferon-a in combination with ribavirin, there is a need to develop drugs that specifically block viral proteins. Highly efficient protease and [...] Read more.
Infection with Hepatitis C Virus (HCV) continues to be a major global health problem. To overcome the limitations of current therapies using interferon-a in combination with ribavirin, there is a need to develop drugs that specifically block viral proteins. Highly efficient protease and polymerase inhibitors are currently undergoing clinical testing and will become available in the next few years. However, with resistance mutations emerging quickly, additional enzymatic activities or functions of HCV have to be targeted by novel compounds. One candidate molecule is the nonstructural protein 2 (NS2), which contains a proteolytic activity that is essential for viral RNA replication. In addition, NS2 is crucial for the assembly of progeny virions and modulates various cellular processes that interfere with viral replication. This review describes the functions of NS2 in the life cycle of HCV and highlights potential antiviral strategies involving NS2. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
Cyclophilin Inhibitors as a Novel HCV Therapy
by Hengli Tang
Viruses 2010, 2(8), 1621-1634; https://doi.org/10.3390/v2081621 - 5 Aug 2010
Cited by 16 | Viewed by 11203
Abstract
A critical role of Cyclophilins, mostly Cyclophilin A (CyPA), in the replication of HCV is supported by a growing body of in vitro and in vivo evidence. CyPA probably interacts directly with nonstructural protein 5A to exert its effect, through its peptidyl-prolyl isomerase [...] Read more.
A critical role of Cyclophilins, mostly Cyclophilin A (CyPA), in the replication of HCV is supported by a growing body of in vitro and in vivo evidence. CyPA probably interacts directly with nonstructural protein 5A to exert its effect, through its peptidyl-prolyl isomerase activity, on maintaining the proper structure and function of the HCV replicase. The major proline substrates are located in domain II of NS5A, centered around a “DY” dipeptide motif that regulates CyPA dependence and CsA resistance. Importantly, Cyclosporine A derivatives that lack immunosuppressive function efficiently block the CyPA-NS5A interaction and inhibit HCV in cell culture, an animal model, and human trials. Given the high genetic barrier to development of resistance and the distinctness of their mechanism from that of either the current standard of care or any specifically targeted antiviral therapy for HCV (STAT-C), CyP inhibitors hold promise as a novel class of anti-HCV therapy. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Review
Macrophages and Cell-Cell Spread of HIV-1
by Kayoko Waki and Eric O. Freed
Viruses 2010, 2(8), 1603-1620; https://doi.org/10.3390/v2081603 - 5 Aug 2010
Cited by 37 | Viewed by 12321
Abstract
Macrophages have been postulated to play an important role in the pathogenesis of HIV-1 infection. Their ability to cross the blood-brain barrier and their resistance to virus-induced cytopathic effects allows them to serve as reservoirs for long-term infection. Thus, exploring the mechanisms of [...] Read more.
Macrophages have been postulated to play an important role in the pathogenesis of HIV-1 infection. Their ability to cross the blood-brain barrier and their resistance to virus-induced cytopathic effects allows them to serve as reservoirs for long-term infection. Thus, exploring the mechanisms of virus transmission from macrophages to target cells such as other macrophages or T lymphocytes is central to our understanding of HIV-1 pathogenesis and progression to AIDS, and is vital to the development of vaccines and novel antiretroviral therapies. This review provides an overview of the current understanding of cell-cell transmission in macrophages. Full article
(This article belongs to the Special Issue Transmission of Retroviruses across Virological Synapses)
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Review
Interferon-λ in HCV Infection and Therapy
by Nicole E. Pagliaccetti and Michael D. Robek
Viruses 2010, 2(8), 1589-1602; https://doi.org/10.3390/v2081589 - 5 Aug 2010
Cited by 26 | Viewed by 12337
Abstract
Chronic infection with hepatitis C virus (HCV) is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG) interferon (IFN)-α and ribavirin. Although this therapy [...] Read more.
Chronic infection with hepatitis C virus (HCV) is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG) interferon (IFN)-α and ribavirin. Although this therapy effectively generates a sustained viral response in approximately half of treated individuals, it is associated with significant hematological and neurological side effects. A new family of IFN-related proteins (IFN-λ1, 2, and 3; or alternately, IL-29, 28A, 28B, respectively) possesses properties that may make these cytokines superior to PEG-IFN-α for HCV therapy. Genetic studies have also implicated these proteins in both the natural and therapy-induced resolution of HCV infection. This review summarizes the basic aspects of IFN-λ biology, the potential role of these cytokines in HCV infection, and the outlook for their therapeutic application. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Article
A VSV-G Pseudotyped Last Generation Lentiviral Vector Mediates High Level and Persistent Gene Transfer in Models of Airway Epithelium In Vitro and In Vivo
by Elena Copreni, Lucia Palmieri, Stefano Castellani and Massimo Conese
Viruses 2010, 2(8), 1577-1588; https://doi.org/10.3390/v2081577 - 2 Aug 2010
Cited by 10 | Viewed by 10681
Abstract
The aim of this work was to evaluate the efficiency and duration of gene expression mediated by a VSV-G pseudotyped last generation lentiviral (LV) vector. We studied LV efficiency in ex-vivo models of respiratory epithelial cells, obtained from bronchial biopsies and nasal polyps, [...] Read more.
The aim of this work was to evaluate the efficiency and duration of gene expression mediated by a VSV-G pseudotyped last generation lentiviral (LV) vector. We studied LV efficiency in ex-vivo models of respiratory epithelial cells, obtained from bronchial biopsies and nasal polyps, by GFP epifluorescence and cytofluorimetry. In vivo efficiency and persistence of gene expression was investigated by GFP immunohistochemistry and luciferase activity in lung cryosections and homogenates, respectively, upon intranasal and intratracheal administration protocols in C57Bl/6 mice. Both primary bronchial and nasal epithelial cells were transduced up to 70-80% 72 hr after the LV infection. In vivo nasal luciferase expression was increased by lysophosphatidylcholine pre-treatment of the nose. Conversely, the bronchial epithelium was transduced in the absence of any pre-conditioning treatment and luciferase expression lasted for at least 6 months without any decline. We conclude that a last generation LV vector is a promising gene transfer agent in the target organ of genetic and acquired lung diseases, as in the case of cystic fibrosis. Full article
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Commentary
Multitasking: Making the Most out of the Retroviral Envelope
by Mariana Varela and Massimo Palmarini
Viruses 2010, 2(8), 1571-1576; https://doi.org/10.3390/v2081571 - 2 Aug 2010
Cited by 2 | Viewed by 8137
Abstract
Evasion of the host’s immune system is a required step for the establishment of viral infection. In this article, we discuss the recent findings of Heidmann and colleagues demonstrating that some retroviruses possess an immune suppressive (IS) domain "encrypted" within their envelope glycoprotein [...] Read more.
Evasion of the host’s immune system is a required step for the establishment of viral infection. In this article, we discuss the recent findings of Heidmann and colleagues demonstrating that some retroviruses possess an immune suppressive (IS) domain "encrypted" within their envelope glycoprotein that is required to establish a successful infection in immunocompetent hosts [1]. Full article
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Short Note
Is there Emergence of Clinical HBV Resistance Under Long-Term HBV Combination Therapy? A Challenging Case Report
by Knud Schewe, Christian Noah, Hüseyin Sirma, Stefan Schmiedel, Jan Van Lunzen, Jürgen Kurt Rockstroh and Oliver Schildgen
Viruses 2010, 2(8), 1564-1570; https://doi.org/10.3390/v2081564 - 29 Jul 2010
Cited by 1 | Viewed by 9469
Abstract
A first case of clinical tenofovir (TDF) HBV resistance in an HIV/HBV coinfected patient who developed an acute flare of hepatitis B is reported. The clinical course was accompanied by signs of acute liver failure after being on successful HBV treatment with tenofovir [...] Read more.
A first case of clinical tenofovir (TDF) HBV resistance in an HIV/HBV coinfected patient who developed an acute flare of hepatitis B is reported. The clinical course was accompanied by signs of acute liver failure after being on successful HBV treatment with tenofovir and persistently undetectable HBV-DNA viral load for over five years. Full article
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Review
Animal Models for Influenza Virus Pathogenesis and Transmission
by Nicole M. Bouvier and Anice C. Lowen
Viruses 2010, 2(8), 1530-1563; https://doi.org/10.3390/v20801530 - 27 Jul 2010
Cited by 289 | Viewed by 19784
Abstract
Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, [...] Read more.
Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein. Full article
(This article belongs to the Special Issue Antivirals Against Influenza)
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Review
Combination Chemotherapy for Influenza
by Elena A. Govorkova and Robert G. Webster
Viruses 2010, 2(8), 1510-1529; https://doi.org/10.3390/v2081510 - 27 Jul 2010
Cited by 64 | Viewed by 17728
Abstract
The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and [...] Read more.
The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir) and to M2 ion channel blockers (amantadine and rimantadine), although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease), the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets. Full article
(This article belongs to the Special Issue Antivirals Against Influenza)
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Editorial
Hepatitis B and C Viruses and Hepatocellular Carcinoma
by Birke Bartosch
Viruses 2010, 2(8), 1504-1509; https://doi.org/10.3390/v2081504 - 27 Jul 2010
Cited by 39 | Viewed by 10729
Abstract
Chronic liver disease is responsible for over 1.4 million deaths annually [1] and is characterized by permanent inflammatory processes that predispose to liver cancer and in particular hepatocellular carcinoma (HCC). In healthy liver, inflammatory processes stimulate growth and repair and restore normal liver [...] Read more.
Chronic liver disease is responsible for over 1.4 million deaths annually [1] and is characterized by permanent inflammatory processes that predispose to liver cancer and in particular hepatocellular carcinoma (HCC). In healthy liver, inflammatory processes stimulate growth and repair and restore normal liver architecture. However, if liver inflammation becomes chronic, the balance of damage versus regeneration in the liver is disrupted and can lead to the formation of excessive scar tissue, termed fibrosis. In the long-term, an exacerbation of fibrosis will lead to cirrhosis, which is characterized by abnormal liver architecture and function and is associated with a significant reduction in overall health and wellbeing. At cirrhotic stages, liver damage is often irreversible or difficult to treat. Cirrhosis leads frequently to death from liver failure or to HCC (Figure 1). Indeed, HCC is the first cause of death in cirrhotic patients [2], and is a tumor with poor prognosis, ranking third in terms of death by cancer. Furthermore, it is the fifth most prevalent cancer worldwide, with 800,000 new cases per year in the world [2,3]. [...] Full article
(This article belongs to the Special Issue Hepatitis Viruses)
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