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Viruses, Volume 3, Issue 1 (January 2011) – 6 articles , Pages 1-62

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660 KiB  
Review
Efficacy of CMX001 as a Post Exposure Antiviral in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans
by Amanda D. Rice, Mathew M. Adams, Greg Wallace, Andrew M. Burrage, Scott F. Lindsey, Andrew J. Smith, Daniele Swetnam, Brandi R. Manning, Stacey A. Gray, Bernhard Lampert, Scott Foster, Randall Lanier, Alice Robertson, George Painter and Richard W. Moyer
Viruses 2011, 3(1), 47-62; https://doi.org/10.3390/v3010047 - 24 Jan 2011
Cited by 55 | Viewed by 7239
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. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the [...] 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. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission), we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model. Full article
(This article belongs to the Special Issue Antivirals Against Poxviruses)
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217 KiB  
Commentary
Another Really, Really Big Virus
by James L. Van Etten
Viruses 2011, 3(1), 32-46; https://doi.org/10.3390/v3010032 - 18 Jan 2011
Cited by 20 | Viewed by 7474
Abstract
Viruses with genomes larger than 300 kb and up to 1.2 Mb, which encode hundreds of proteins, are being discovered and characterized with increasing frequency. Most, but not all, of these large viruses (often referred to as giruses) infect protists that live in [...] Read more.
Viruses with genomes larger than 300 kb and up to 1.2 Mb, which encode hundreds of proteins, are being discovered and characterized with increasing frequency. Most, but not all, of these large viruses (often referred to as giruses) infect protists that live in aqueous environments. Bioinformatic analyses of metagenomes of aqueous samples indicate that large DNA viruses are quite common in nature and await discovery. One issue that is perhaps not appreciated by the virology community is that large viruses, even those classified in the same family, can differ significantly in morphology, lifestyle, and gene complement. This brief commentary, which will mention some of these unique properties, was stimulated by the characterization of the newest member of this club, virus CroV (Fischer, M.G.; Allen, M.J.; Wilson, W.H.; Suttle, C.A. Giant virus with a remarkable complement of genes infects marine zooplankton. Proc. Natl. Acad. Sci. USA 2010, 107, 19508-19513 [1]). CroV has a 730 kb genome (with ~544 protein-encoding genes) and infects the marine microzooplankton Cafeteria roenbergensis producing a lytic infection. Full article
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146 KiB  
Commentary
Un-“ESCRT”-ed Budding
by Mark Yondola and Carol Carter
Viruses 2011, 3(1), 26-31; https://doi.org/10.3390/v3010026 - 18 Jan 2011
Cited by 2 | Viewed by 5738
Abstract
In their recent publication, Rossman et al. [1] describe how the inherent budding capability of its M2 protein allows influenza A virus to bypass recruitment of the cellular ESCRT machinery enlisted by several other enveloped RNA and DNA viruses, including HIV, Ebola, rabies, [...] Read more.
In their recent publication, Rossman et al. [1] describe how the inherent budding capability of its M2 protein allows influenza A virus to bypass recruitment of the cellular ESCRT machinery enlisted by several other enveloped RNA and DNA viruses, including HIV, Ebola, rabies, herpes simplex type 1 and hepatitis B. Studies from the same laboratory [2] and other laboratories [3–6] indicate that budding of plasmid-derived virus-like particles can be mediated by the influenza virus hemagglutinin and neuraminidase proteins in the absence of M2. These events are also independent of canonical ESCRT components [2,7]. Understanding how intrinsic properties of these influenza virus proteins permit ESCRT-independent budding expands our understanding of the budding process itself. Full article
162 KiB  
Commentary
Structures of Reverse Transcriptase Pre- and Post-Excision Complexes Shed New Light on HIV-1 AZT Resistance
by Walter A. Scott
Viruses 2011, 3(1), 20-25; https://doi.org/10.3390/v3010020 - 18 Jan 2011
Cited by 7 | Viewed by 4339
Abstract
HIV-1 resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) results from mutations in reverse transcriptase that increase the ability of the enzyme to excise AZT-monophosphate after it has been incorporated. Crystal structures of complexes of wild type and mutant reverse transcriptase with double-stranded DNA with or [...] Read more.
HIV-1 resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) results from mutations in reverse transcriptase that increase the ability of the enzyme to excise AZT-monophosphate after it has been incorporated. Crystal structures of complexes of wild type and mutant reverse transcriptase with double-stranded DNA with or without the excision product, AZT adenosine dinucleoside tetraphosphate (AZTppppA), have recently been reported [1]. The excision-enhancing mutations dramatically change the way the enzyme interacts with the excision product. Full article
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Commentary
Changes in Population Dynamics in Mutualistic versus Pathogenic Viruses
by Marilyn J. Roossinck
Viruses 2011, 3(1), 12-19; https://doi.org/10.3390/v3010012 - 17 Jan 2011
Cited by 11 | Viewed by 6407
Abstract
Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of [...] Read more.
Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics. Full article
(This article belongs to the Special Issue Virus Dynamics and Evolution)
397 KiB  
Review
Rev Variation during Persistent Lentivirus Infection
by Susan Carpenter, Wei-Chen Chen and Karin S. Dorman
Viruses 2011, 3(1), 1-11; https://doi.org/10.3390/v3010001 - 11 Jan 2011
Cited by 7 | Viewed by 5890
Abstract
The ability of lentiviruses to continually evolve and escape immune control is the central impediment in developing an effective vaccine for HIV-1 and other lentiviruses. Equine infectious anemia virus (EIAV) is considered a useful model for immune control of lentivirus infection. Virus-specific cytotoxic [...] Read more.
The ability of lentiviruses to continually evolve and escape immune control is the central impediment in developing an effective vaccine for HIV-1 and other lentiviruses. Equine infectious anemia virus (EIAV) is considered a useful model for immune control of lentivirus infection. Virus-specific cytotoxic T lymphocytes (CTL) and broadly neutralizing antibody effectively control EIAV replication during inapparent stages of disease, but after years of low-level replication, the virus is still able to produce evasion genotypes that lead to late re-emergence of disease. There is a high rate of genetic variation in the EIAV surface envelope glycoprotein (SU) and in the region of the transmembrane protein (TM) overlapped by the major exon of Rev. This review examines genetic and phenotypic variation in Rev during EIAV disease and a possible role for Rev in immune evasion and virus persistence. Full article
(This article belongs to the Special Issue Virus Dynamics and Evolution)
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