Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions.
PLoS One
; 4(10): e7514, 2009 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-19838296
ABSTRACT
Although HIV-1 Vpr displays several functions in vitro, limited information exists concerning their relevance during infection. Here, we characterized Vpr variants isolated from a rapid and a long-term non-progressor (LTNP). Interestingly, vpr alleles isolated from longitudinal samples of the LTNP revealed a dominant sequence that subsequently led to diversity similar to that observed in the progressor patient. Most of primary Vpr proteins accumulated at the nuclear envelope and interacted with host-cell partners of Vpr. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Genes vpr
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Produtos do Gene vpr
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Sequências Repetidas Terminais
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Produtos do Gene vpr do Vírus da Imunodeficiência Humana
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article