Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count

Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count

Author Bizinoto, Maria Clara Autor UNIFESP Google Scholar
Yabe, Shiori Google Scholar
Leal, Elcio Google Scholar
Kishino, Hirohisa Google Scholar
Martins, Leonardo de Oliveira Google Scholar
Lima, Mariana Leão de Autor UNIFESP Google Scholar
Morais, Edsel Renata Autor UNIFESP Google Scholar
Diaz, Ricardo Sobhie Autor UNIFESP Google Scholar
Janini, Luiz Mario Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Tokyo
Fed Univ Para
Univ Vigo
Abstract Background: the human APOBEC3G (A3G) protein activity is associated with innate immunity against HIV-1 by inducing high rates of guanosines to adenosines (G-to-A) mutations (viz., hypermutation) in the viral DNA. If hypermutation is not enough to disrupt the reading frames of viral genes, it may likely increase the HIV-1 diversity. To counteract host innate immunity HIV-1 encodes the Vif protein that binds A3G protein and form complexes to be degraded by cellular proteolysis.Methods: Here we studied the pattern of substitutions in the vif gene and its association with clinical status of HIV-1 infected individuals. To perform the study, unique vif gene sequences were generated from 400 antiretroviral-naive individuals.Results: the codon pairs: 78-154, 85-154, 101-157, 105-157, and 105-176 of vif gene were associated with CD4+ T cell count lower than 500 cells per mm(3). Some of these codons were located in the (81)LGQGVSIEW(89) region and within the BC-Box. We also identified codons under positive selection clustered in the N-terminal region of Vif protein, between (WKSLVK26)-W-21 and (YRHHY44)-Y-40 regions (i.e., 31, 33, 37, 39), within the BC-Box (i.e., 155, 159) and the Cullin5-Box (i.e., 168) of vif gene. All these regions are involved in the Vif-induced degradation of A3G/F complexes and the N-terminal of Vif protein binds to viral and cellular RNA.Conclusions: Adaptive evolution of vif gene was mostly to optimize viral RNA binding and A3G/F recognition. Additionally, since there is not a fully resolved structure of the Vif protein, codon pairs associated with CD4+ T cell count may elucidate key regions that interact with host cell factors. Here we identified and discriminated codons under positive selection and codons under functional constraint in the vif gene of HIV-1.
Keywords HIV-1
Epistasis
APOBEC
Vif
Hypermutation
Positive selection
Co-evolution
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Japan Society for the Promotion of Science (SPS KAKENHI)
Grant number FAPESP: 06/50109-5
Japan Society for the Promotion of Science (SPS KAKENHI): 19300094
Date 2013-04-11
Published in Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 10 p., 2013.
ISSN 1471-2334 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 10
Origin http://dx.doi.org/10.1186/1471-2334-13-173
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000318559900002
URI http://repositorio.unifesp.br/handle/11600/36202

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