dc.contributor.author |
Santos, André Felipe Andrade dos |
|
dc.contributor.author |
Lengruber, Renan Bohrer |
|
dc.contributor.author |
Soares, Esmeralda Augusta Jardim Machado |
|
dc.contributor.author |
Jere, Abhay |
|
dc.contributor.author |
Sprinz, Eduardo |
|
dc.contributor.author |
Martinez, Ana Maria Barral de |
|
dc.contributor.author |
Silveira, Jussara Maria |
|
dc.contributor.author |
Sion, Fernando Samuel |
|
dc.contributor.author |
Pathak, Vinay Kumar |
|
dc.contributor.author |
Soares, Marcelo Alves |
|
dc.date.accessioned |
2013-06-06T13:33:30Z |
|
dc.date.available |
2013-06-06T13:33:30Z |
|
dc.date.issued |
2008 |
|
dc.identifier.citation |
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. |
pt_BR |
dc.identifier.uri |
http://repositorio.furg.br/handle/1/3469 |
|
dc.description.abstract |
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. |
pt_BR |
dc.language.iso |
eng |
pt_BR |
dc.rights |
open access |
pt_BR |
dc.title |
Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI- treated patients |
pt_BR |
dc.type |
article |
pt_BR |