Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal
Autor(a) principal: | |
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Data de Publicação: | 2003 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/1586 |
Resumo: | Human immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but nef has been implicated in inducing a more pathogenic phenotype in vivo. However, relatively little is known about the role of nef in HIV-2 pathogenesis. To address this, the genetic composition of 44 nef alleles from 37 HIV-2-infected individuals in Portugal, encompassing a wide spectrum of disease associations, CD4 counts and virus load, has been assessed. All nef alleles were subtype A, with no evidence of gross deletions, truncations or disruptions in the nef-encoding sequence; all were full-length and intact. HIV-2 long terminal repeat sequences were conserved and also indicated subtype A infections. Detailed analysis of motifs that mediate nef function in HIV-1 and simian immunodeficiency virus, such as CD4 downregulation and putative SH2/SH3 interactions, revealed significant natural variation. In particular, the central P(104)xxPLR motif exhibited wide interpatient variation, ranging from an HIV-1-like tetra-proline structure (PxxP)(3) to a disrupted minimal core motif (P(104)xxQLR). The P(107)-->Q substitution was associated with an asymptomatic phenotype (Fisher's exact test, P=0.026) and low virus loads. These data indicate that discrete differences in the nef gene sequence rather than gross structural changes are more likely to play a role in HIV-2 pathogenesis mediated via specific functional interactions. |
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Natural variation of the nef gene in human immunodeficiency virus type 2 infections in PortugalHIV-2Nef GeneNatural VariationPortugalInfecções Sexualmente TransmissíveisHuman immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but nef has been implicated in inducing a more pathogenic phenotype in vivo. However, relatively little is known about the role of nef in HIV-2 pathogenesis. To address this, the genetic composition of 44 nef alleles from 37 HIV-2-infected individuals in Portugal, encompassing a wide spectrum of disease associations, CD4 counts and virus load, has been assessed. All nef alleles were subtype A, with no evidence of gross deletions, truncations or disruptions in the nef-encoding sequence; all were full-length and intact. HIV-2 long terminal repeat sequences were conserved and also indicated subtype A infections. Detailed analysis of motifs that mediate nef function in HIV-1 and simian immunodeficiency virus, such as CD4 downregulation and putative SH2/SH3 interactions, revealed significant natural variation. In particular, the central P(104)xxPLR motif exhibited wide interpatient variation, ranging from an HIV-1-like tetra-proline structure (PxxP)(3) to a disrupted minimal core motif (P(104)xxQLR). The P(107)-->Q substitution was associated with an asymptomatic phenotype (Fisher's exact test, P=0.026) and low virus loads. These data indicate that discrete differences in the nef gene sequence rather than gross structural changes are more likely to play a role in HIV-2 pathogenesis mediated via specific functional interactions.Repositório Científico do Instituto Nacional de SaúdePádua, E.Jenkins, A.Brown, S.Bootman, J.Paixão, M.T.Almond, N.Berry, N.2013-05-24T17:08:18Z2003-052003-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/1586engJ Gen Virol. 2003 May;84(Pt 5):1287-99doi: 10.1099/vir.0.18908-0info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:38:48ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
title |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
spellingShingle |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal Pádua, E. HIV-2 Nef Gene Natural Variation Portugal Infecções Sexualmente Transmissíveis |
title_short |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
title_full |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
title_fullStr |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
title_full_unstemmed |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
title_sort |
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal |
author |
Pádua, E. |
author_facet |
Pádua, E. Jenkins, A. Brown, S. Bootman, J. Paixão, M.T. Almond, N. Berry, N. |
author_role |
author |
author2 |
Jenkins, A. Brown, S. Bootman, J. Paixão, M.T. Almond, N. Berry, N. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Pádua, E. Jenkins, A. Brown, S. Bootman, J. Paixão, M.T. Almond, N. Berry, N. |
dc.subject.por.fl_str_mv |
HIV-2 Nef Gene Natural Variation Portugal Infecções Sexualmente Transmissíveis |
topic |
HIV-2 Nef Gene Natural Variation Portugal Infecções Sexualmente Transmissíveis |
description |
Human immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but nef has been implicated in inducing a more pathogenic phenotype in vivo. However, relatively little is known about the role of nef in HIV-2 pathogenesis. To address this, the genetic composition of 44 nef alleles from 37 HIV-2-infected individuals in Portugal, encompassing a wide spectrum of disease associations, CD4 counts and virus load, has been assessed. All nef alleles were subtype A, with no evidence of gross deletions, truncations or disruptions in the nef-encoding sequence; all were full-length and intact. HIV-2 long terminal repeat sequences were conserved and also indicated subtype A infections. Detailed analysis of motifs that mediate nef function in HIV-1 and simian immunodeficiency virus, such as CD4 downregulation and putative SH2/SH3 interactions, revealed significant natural variation. In particular, the central P(104)xxPLR motif exhibited wide interpatient variation, ranging from an HIV-1-like tetra-proline structure (PxxP)(3) to a disrupted minimal core motif (P(104)xxQLR). The P(107)-->Q substitution was associated with an asymptomatic phenotype (Fisher's exact test, P=0.026) and low virus loads. These data indicate that discrete differences in the nef gene sequence rather than gross structural changes are more likely to play a role in HIV-2 pathogenesis mediated via specific functional interactions. |
publishDate |
2003 |
dc.date.none.fl_str_mv |
2003-05 2003-05-01T00:00:00Z 2013-05-24T17:08:18Z |
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.uri.fl_str_mv |
http://hdl.handle.net/10400.18/1586 |
url |
http://hdl.handle.net/10400.18/1586 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Gen Virol. 2003 May;84(Pt 5):1287-99 doi: 10.1099/vir.0.18908-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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1777303617949138944 |