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

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dc.contributor.authorBizinoto, Maria Clara [UNIFESP]
dc.contributor.authorYabe, Shiori
dc.contributor.authorLeal, Elcio
dc.contributor.authorKishino, Hirohisa
dc.contributor.authorMartins, Leonardo de Oliveira
dc.contributor.authorDe Lima-Stein, Mariana Leão [UNIFESP]
dc.contributor.authorMorais, Edsel Renata [UNIFESP]
dc.contributor.authorDiaz, Ricardo Sobhie [UNIFESP]
dc.contributor.authorJanini, Luiz Mario [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Tokyo
dc.contributor.institutionFed Univ Para
dc.contributor.institutionUniv Vigo
dc.date.accessioned2016-01-24T14:31:34Z
dc.date.available2016-01-24T14:31:34Z
dc.date.issued2013-04-11
dc.description.abstractBackground: 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.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, São Paulo, Brazil
dc.description.affiliationUniv Tokyo, Grad Sch Agr & Life Sci, Tokyo, Japan
dc.description.affiliationFed Univ Para, Inst Biotechnol, BR-66059 Belem, Para, Brazil
dc.description.affiliationUniv Vigo, Dept Biochem Genet & Immunol, Bioinformat & Mol Evolut Lab, Vigo 36310, Spain
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, São Paulo, Brazil
dc.description.provenanceMade available in DSpace on 2016-01-24T14:31:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-04-11. Added 1 bitstream(s) on 2016-01-31T13:36:57Z : No. of bitstreams: 1 WOS000318559900002.pdf: 2342212 bytes, checksum: ecd47bec42d5f7d41487bc46ea1f6c18 (MD5)en
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipJapan Society for the Promotion of Science (SPS KAKENHI)
dc.description.sponsorshipIDFAPESP: 06/50109-5pt
dc.description.sponsorshipIDJapan Society for the Promotion of Science (SPS KAKENHI): 19300094
dc.format.extent10
dc.identifierhttps://dx.doi.org/10.1186/1471-2334-13-173
dc.identifier.citationBmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 10 p., 2013.
dc.identifier.doi10.1186/1471-2334-13-173
dc.identifier.fileWOS000318559900002.pdf
dc.identifier.issn1471-2334
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/36202
dc.identifier.wosWOS:000318559900002
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Infectious Diseases
dc.rightsAcesso aberto
dc.subjectHIV-1en
dc.subjectEpistasisen
dc.subjectAPOBECen
dc.subjectVifen
dc.subjectHypermutationen
dc.subjectPositive selectionen
dc.subjectCo-evolutionen
dc.titleCodon pairs of the HIV-1 vif gene correlate with CD4+T cell counten
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