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Viruses, Volume 3, Issue 2 (February 2011) – 6 articles , Pages 63-171

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Research

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221 KiB  
Article
Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation
by Abby Harrison, Philippe Lemey, Matthew Hurles, Chris Moyes, Susanne Horn, Jan Pryor, Joji Malani, Mathias Supuri, Andrew Masta, Burentau Teriboriki, Tebuka Toatu, David Penny, Andrew Rambaut and Beth Shapiro
Viruses 2011, 3(2), 83-101; https://doi.org/10.3390/v3020083 - 25 Jan 2011
Cited by 46 | Viewed by 9064
Abstract
Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the [...] Read more.
Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements. Full article
(This article belongs to the Special Issue Virus Dynamics and Evolution)
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Review

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1335 KiB  
Review
Efficacy of CMX001 as a Prophylactic and Presymptomatic Antiviral Agent in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans
by Amanda D. Rice, Mathew M. Adams, Bernhard Lampert, Scott Foster, Randall Lanier, Alice Robertson, George Painter and Richard W. Moyer
Viruses 2011, 3(2), 63-82; https://doi.org/10.3390/v3020063 - 25 Jan 2011
Cited by 40 | Viewed by 7382
Abstract
CMX001, a lipophilic nucleotide analog formed by covalently linking 3‑(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown [...] Read more.
CMX001, a lipophilic nucleotide analog formed by covalently linking 3‑(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination. Full article
(This article belongs to the Special Issue Antivirals Against Poxviruses)
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293 KiB  
Review
Cytoskeletal Dynamics: Concepts in Measles Virus Replication and Immunomodulation
by Elita Avota, Evelyn Gassert and Sibylle Schneider-Schaulies
Viruses 2011, 3(2), 102-117; https://doi.org/10.3390/v3020102 - 26 Jan 2011
Cited by 8 | Viewed by 5877
Abstract
In common with most viruses, measles virus (MV) relies on the integrity of the cytoskeleton of its host cells both with regard to efficient replication in these cells, but also retention of their motility which favors viral dissemination. It is, however, the surface [...] Read more.
In common with most viruses, measles virus (MV) relies on the integrity of the cytoskeleton of its host cells both with regard to efficient replication in these cells, but also retention of their motility which favors viral dissemination. It is, however, the surface interaction of the viral glycoprotein (gp) complex with receptors present on lymphocytes and dendritic cells (DCs), that signals effective initiation of host cell cytoskeletal dynamics. For DCs, these may act to regulate processes as diverse as viral uptake and sorting, but also the ability of these cells to successfully establish and maintain functional immune synapses (IS) with T cells. In T cells, MV signaling causes actin cytoskeletal paralysis associated with a loss of polarization, adhesion and motility, which has been linked to activation of sphingomyelinases and subsequent accumulation of membrane ceramides. MV modulation of both DC and T cell cytoskeletal dynamics may be important for the understanding of MV immunosuppression at the cellular level. Full article
(This article belongs to the Special Issue Cytoskeleton in Viral Infections)
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286 KiB  
Review
What Has the Study of the K3 and K5 Viral Ubiquitin E3 Ligases Taught Us about Ubiquitin-Mediated Receptor Regulation?
by Jessica M. Boname and Paul J. Lehner
Viruses 2011, 3(2), 118-131; https://doi.org/10.3390/v3020118 - 28 Jan 2011
Cited by 42 | Viewed by 6447
Abstract
Cells communicate with each other and the outside world through surface receptors, which need to be tightly regulated to prevent both overstimulation and receptor desensitization. Understanding the processes involved in the homeostatic control of cell surface receptors is essential, but we are not [...] Read more.
Cells communicate with each other and the outside world through surface receptors, which need to be tightly regulated to prevent both overstimulation and receptor desensitization. Understanding the processes involved in the homeostatic control of cell surface receptors is essential, but we are not alone in trying to regulate these receptors. Viruses, as the ultimate host pathogens, have co-evolved over millions of years and have both pirated and adapted host genes to enable viral pathogenesis. K3 and K5 (also known as MIR1 and MIR2) are viral ubiquitin E3 ligases from Kaposi’s Sarcoma Associated Herpesvirus (KSHV) which decrease expression of a number of cell surface receptors and have been used to interrogate cellular processes and improve our understanding of ubiquitin-mediated receptor endocytosis and degradation. In this review, we summarize what has been learned from the study of these viral genes and emphasize their role in elucidating the complexity of ubiquitin in receptor regulation. Full article
(This article belongs to the Special Issue Viruses and the Ubiquitin/Proteasome System)
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347 KiB  
Review
The Inside Out of Lentiviral Vectors
by Stéphanie Durand and Andrea Cimarelli
Viruses 2011, 3(2), 132-159; https://doi.org/10.3390/v3020132 - 14 Feb 2011
Cited by 59 | Viewed by 9437
Abstract
Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we [...] Read more.
Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them. Full article
(This article belongs to the Special Issue Retroviral Vectors)
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Other

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188 KiB  
Commentary
Flavivirus Cell Entry and Membrane Fusion
by Jolanda M. Smit, Bastiaan Moesker, Izabela Rodenhuis-Zybert and Jan Wilschut
Viruses 2011, 3(2), 160-171; https://doi.org/10.3390/v3020160 - 22 Feb 2011
Cited by 226 | Viewed by 10339
Abstract
Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent [...] Read more.
Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advances in the understanding of flavivirus cell entry with specific emphasis on the recent study of Zaitseva and coworkers, indicating that anionic lipids might play a crucial role in the fusion process of dengue virus [1]. Full article
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