Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FURG (RI FURG) |
Texto Completo: | http://repositorio.furg.br/handle/1/3469 |
Resumo: | Background: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naıve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher’s exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions. |
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Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patientsBackground: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naıve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher’s exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.2013-06-06T13:33:30Z2013-06-06T13:33:30Z2008info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfSANTOS, André Felipe Andrade dos et al. Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients. Plos One, v. 3, n. 3, p. 01-07, 2008. Disponível em: <http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0001781&representation=PDF>. Acesso em: 27 ago. 2012.http://repositorio.furg.br/handle/1/3469engSantos, André Felipe Andrade dosLengruber, Renan BohrerSoares, Esmeralda Augusta Jardim MachadoJere, AbhaySprinz, EduardoMartinez, Ana Maria Barral deSilveira, Jussara MariaSion, Fernando SamuelPathak, Vinay KumarSoares, Marcelo Alvesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FURG (RI FURG)instname:Universidade Federal do Rio Grande (FURG)instacron:FURG2013-06-06T13:33:30Zoai:repositorio.furg.br:1/3469Repositório InstitucionalPUBhttps://repositorio.furg.br/oai/request || http://200.19.254.174/oai/requestopendoar:2013-06-06T13:33:30Repositório Institucional da FURG (RI FURG) - Universidade Federal do Rio Grande (FURG)false |
dc.title.none.fl_str_mv |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
title |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
spellingShingle |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients Santos, André Felipe Andrade dos |
title_short |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
title_full |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
title_fullStr |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
title_full_unstemmed |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
title_sort |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
author |
Santos, André Felipe Andrade dos |
author_facet |
Santos, André Felipe Andrade dos Lengruber, Renan Bohrer Soares, Esmeralda Augusta Jardim Machado Jere, Abhay Sprinz, Eduardo Martinez, Ana Maria Barral de Silveira, Jussara Maria Sion, Fernando Samuel Pathak, Vinay Kumar Soares, Marcelo Alves |
author_role |
author |
author2 |
Lengruber, Renan Bohrer Soares, Esmeralda Augusta Jardim Machado Jere, Abhay Sprinz, Eduardo Martinez, Ana Maria Barral de Silveira, Jussara Maria Sion, Fernando Samuel Pathak, Vinay Kumar Soares, Marcelo Alves |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Santos, André Felipe Andrade dos Lengruber, Renan Bohrer Soares, Esmeralda Augusta Jardim Machado Jere, Abhay Sprinz, Eduardo Martinez, Ana Maria Barral de Silveira, Jussara Maria Sion, Fernando Samuel Pathak, Vinay Kumar Soares, Marcelo Alves |
description |
Background: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naıve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher’s exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008 2013-06-06T13:33:30Z 2013-06-06T13:33:30Z |
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 |
SANTOS, André Felipe Andrade dos et al. Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients. Plos One, v. 3, n. 3, p. 01-07, 2008. Disponível em: <http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0001781&representation=PDF>. Acesso em: 27 ago. 2012. http://repositorio.furg.br/handle/1/3469 |
identifier_str_mv |
SANTOS, André Felipe Andrade dos et al. Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients. Plos One, v. 3, n. 3, p. 01-07, 2008. Disponível em: <http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0001781&representation=PDF>. Acesso em: 27 ago. 2012. |
url |
http://repositorio.furg.br/handle/1/3469 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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 Institucional da FURG (RI FURG) instname:Universidade Federal do Rio Grande (FURG) instacron:FURG |
instname_str |
Universidade Federal do Rio Grande (FURG) |
instacron_str |
FURG |
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FURG |
reponame_str |
Repositório Institucional da FURG (RI FURG) |
collection |
Repositório Institucional da FURG (RI FURG) |
repository.name.fl_str_mv |
Repositório Institucional da FURG (RI FURG) - Universidade Federal do Rio Grande (FURG) |
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