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      Rev Variation during Persistent Lentivirus Infection

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          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 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.

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          Most cited references30

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          Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.

          Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The "neutral model" assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The "positive-selection model" assumes an additional category of positively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identify target sites for positive selection. The models are applied to a data set of the V3 region of the HIV-1 envelope gene, sequenced at different years after the infection of one patient. The results provide strong support for variable selection intensity among amino acid sites The neutral model is rejected in favor of the positive-selection model, indicating the operation of positive selection in the region. Positively selected sites are found in both the V3 region and the flanking regions.
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            A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome.

            A model of DNA sequence evolution applicable to coding regions is presented. This represents the first evolutionary model that accounts for dependencies among nucleotides within a codon. The model uses the codon, as opposed to the nucleotide, as the unit of evolution, and is parameterized in terms of synonymous and nonsynonymous nucleotide substitution rates. One of the model's advantages over those used in methods for estimating synonymous and nonsynonymous substitution rates is that it completely corrects for multiple hits at a codon, rather than taking a parsimony approach and considering only pathways of minimum change between homologous codons. Likelihood-ratio versions of the relative-rate test are constructed and applied to data from the complete chloroplast DNA sequences of Oryza sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these tests confirm previous findings that substitution rates in the chloroplast genome are subject to both lineage-specific and locus-specific effects. Additionally, the new tests suggest tha the rate heterogeneity is due primarily to differences in nonsynonymous substitution rates. Simulations help confirm previous suggestions that silent sites are saturated, leaving no evidence of heterogeneity in synonymous substitution rates.
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              A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes.

              W Li, C. Wu, C Luo (1985)
              A new method is proposed for estimating the number of synonymous and nonsynonymous nucleotide substitutions between homologous genes. In this method, a nucleotide site is classified as nondegenerate, twofold degenerate, or fourfold degenerate, depending on how often nucleotide substitutions will result in amino acid replacement; nucleotide changes are classified as either transitional or transversional, and changes between codons are assumed to occur with different probabilities, which are determined by their relative frequencies among more than 3,000 changes in mammalian genes. The method is applied to a large number of mammalian genes. The rate of nonsynonymous substitution is extremely variable among genes; it ranges from 0.004 X 10(-9) (histone H4) to 2.80 X 10(-9) (interferon gamma), with a mean of 0.88 X 10(-9) substitutions per nonsynonymous site per year. The rate of synonymous substitution is also variable among genes; the highest rate is three to four times higher than the lowest one, with a mean of 4.7 X 10(-9) substitutions per synonymous site per year. The rate of nucleotide substitution is lowest at nondegenerate sites (the average being 0.94 X 10(-9), intermediate at twofold degenerate sites (2.26 X 10(-9)). and highest at fourfold degenerate sites (4.2 X 10(-9)). The implication of our results for the mechanisms of DNA evolution and that of the relative likelihood of codon interchanges in parsimonious phylogenetic reconstruction are discussed.
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                Author and article information

                Journal
                Viruses
                Viruses
                Molecular Diversity Preservation International (MDPI)
                1999-4915
                January 2011
                11 January 2011
                : 3
                : 1
                : 1-11
                Affiliations
                [1 ]Department of Animal Science, Iowa State University, Ames, IA 50011-3260, USA
                [2 ]Department of Statistics, Iowa State University, Ames, IA 50011-1210, USA; E-Mail: snoweye@ 123456iastate.edu (W.-C.C.)
                [3 ]Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011-3260, USA; E-Mail: kdorman@ 123456iastate.edu
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: scarp@ 123456iastate.edu ; Tel.: +1-515-294-5694; Fax: +1-515-294-0453.
                Article
                viruses-03-00001
                10.3390/v3010001
                3187595
                21994723
                b7cbb612-2f18-4354-a6e7-0054c8ea2dc6
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 20 November 2010
                : 29 December 2010
                : 6 January 2011
                Categories
                Review

                Microbiology & Virology
                rev,lentivirus,immune evasion,overlapping reading frames,selection,equine infectious anemia virus

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