Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/36202 https://dx.doi.org/10.1186/1471-2334-13-173 |
Resumo: | 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. |
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Bizinoto, Maria Clara [UNIFESP]Yabe, ShioriLeal, ElcioKishino, HirohisaMartins, Leonardo de OliveiraDe Lima-Stein, Mariana Leão [UNIFESP]Morais, Edsel Renata [UNIFESP]Diaz, Ricardo Sobhie [UNIFESP]Janini, Luiz Mario [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Univ TokyoFed Univ ParaUniv Vigo2016-01-24T14:31:34Z2016-01-24T14:31:34Z2013-04-11Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 10 p., 2013.1471-2334https://repositorio.unifesp.br/handle/11600/36202https://dx.doi.org/10.1186/1471-2334-13-173WOS000318559900002.pdf10.1186/1471-2334-13-173WOS:000318559900002Background: 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Japan Society for the Promotion of Science (SPS KAKENHI)Universidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniv Tokyo, Grad Sch Agr & Life Sci, Tokyo, JapanFed Univ Para, Inst Biotechnol, BR-66059 Belem, Para, BrazilUniv Vigo, Dept Biochem Genet & Immunol, Bioinformat & Mol Evolut Lab, Vigo 36310, SpainUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilFAPESP: 06/50109-5Japan Society for the Promotion of Science (SPS KAKENHI): 19300094Web of Science10engBiomed Central LtdBmc Infectious DiseasesHIV-1EpistasisAPOBECVifHypermutationPositive selectionCo-evolutionCodon pairs of the HIV-1 vif gene correlate with CD4+T cell countinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000318559900002.pdfapplication/pdf2342212${dspace.ui.url}/bitstream/11600/36202/1/WOS000318559900002.pdfecd47bec42d5f7d41487bc46ea1f6c18MD51open accessTEXTWOS000318559900002.pdf.txtWOS000318559900002.pdf.txtExtracted texttext/plain42090${dspace.ui.url}/bitstream/11600/36202/2/WOS000318559900002.pdf.txtab7c50c057261473c51b30ce4973bcd4MD52open access11600/362022022-10-11 18:55:08.185open accessoai:repositorio.unifesp.br:11600/36202Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-10-11T21:55:08Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
title |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
spellingShingle |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count Bizinoto, Maria Clara [UNIFESP] HIV-1 Epistasis APOBEC Vif Hypermutation Positive selection Co-evolution |
title_short |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
title_full |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
title_fullStr |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
title_full_unstemmed |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
title_sort |
Codon pairs of the HIV-1 vif gene correlate with CD4+T cell count |
author |
Bizinoto, Maria Clara [UNIFESP] |
author_facet |
Bizinoto, Maria Clara [UNIFESP] Yabe, Shiori Leal, Elcio Kishino, Hirohisa Martins, Leonardo de Oliveira De Lima-Stein, Mariana Leão [UNIFESP] Morais, Edsel Renata [UNIFESP] Diaz, Ricardo Sobhie [UNIFESP] Janini, Luiz Mario [UNIFESP] |
author_role |
author |
author2 |
Yabe, Shiori Leal, Elcio Kishino, Hirohisa Martins, Leonardo de Oliveira De Lima-Stein, Mariana Leão [UNIFESP] Morais, Edsel Renata [UNIFESP] Diaz, Ricardo Sobhie [UNIFESP] Janini, Luiz Mario [UNIFESP] |
author2_role |
author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Univ Tokyo Fed Univ Para Univ Vigo |
dc.contributor.author.fl_str_mv |
Bizinoto, Maria Clara [UNIFESP] Yabe, Shiori Leal, Elcio Kishino, Hirohisa Martins, Leonardo de Oliveira De Lima-Stein, Mariana Leão [UNIFESP] Morais, Edsel Renata [UNIFESP] Diaz, Ricardo Sobhie [UNIFESP] Janini, Luiz Mario [UNIFESP] |
dc.subject.eng.fl_str_mv |
HIV-1 Epistasis APOBEC Vif Hypermutation Positive selection Co-evolution |
topic |
HIV-1 Epistasis APOBEC Vif Hypermutation Positive selection Co-evolution |
description |
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. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-04-11 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:31:34Z |
dc.date.available.fl_str_mv |
2016-01-24T14:31:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 10 p., 2013. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/36202 https://dx.doi.org/10.1186/1471-2334-13-173 |
dc.identifier.issn.none.fl_str_mv |
1471-2334 |
dc.identifier.file.none.fl_str_mv |
WOS000318559900002.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/1471-2334-13-173 |
dc.identifier.wos.none.fl_str_mv |
WOS:000318559900002 |
identifier_str_mv |
Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 10 p., 2013. 1471-2334 WOS000318559900002.pdf 10.1186/1471-2334-13-173 WOS:000318559900002 |
url |
https://repositorio.unifesp.br/handle/11600/36202 https://dx.doi.org/10.1186/1471-2334-13-173 |
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eng |
language |
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Bmc Infectious Diseases |
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openAccess |
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10 |
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Biomed Central Ltd |
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Biomed Central Ltd |
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