Impaired viral entry cannot explain reduced CD4+ T cell susceptibility to HIV type 1 in certain highly exposed individuals.
AIDS Res Hum Retroviruses
; 24(11): 1415-27, 2008 Nov.
Article
em En
| MEDLINE
| ID: mdl-19000021
ABSTRACT
Rare individuals report repeated unprotected HIV-1 sexual exposures, yet remain seronegative for years. We investigated the possibility that reduced in vitro CD4(+) T cell susceptibility to HIV-1 infection protects such highly exposed seronegative (ES) individuals. Susceptibility to three R5-tropic HIV-1 isolates, regardless of inoculating dose, was remarkably similar between 81 ES and 33 low-risk controls. In 94% (99/105) of donors, we observed a 1.36 log-unit range in HIV-1(JR-CSF) production, with similar results for HIV-1(1192). The median frequency of intracellular Gag(+) T cells after single-round infection was similar in ES (5.2%) and controls (7.2%), p = 0.456. However, in repeated testing, CD4(+) T cells from two controls (6.1%) and four ES (4.9%) exhibited a 10- to 2500-fold reduction in HIV-1 production and required 5- to 12-fold greater HIV-1(1192) and HIV-1(JR-CSF) inocula to establish infection (TCID(50)). Reduced viral entry cannot explain the low producer phenotype; no differences in CCR5 receptor density or beta-chemokine production were observed. In conclusion, we have identified a remarkably narrow range of HIV-1 susceptibility in seronegative donors regardless of risk activity, which can be applied as a benchmark to assess vaccine-induced antiviral effector activities. However, CD4(+) T cells from a subset of individuals demonstrated reduced HIV-1 susceptibility unexplained by impaired entry, lending support to the possibility that cellular restriction of HIV-1 may account for continued seronegativity in some of those having repeated sexual exposure. Identifying the host-virus interactions responsible for diminished in vitro susceptibility may contribute to the development of novel therapeutic strategies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Infecções por HIV
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HIV-1
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Internalização do Vírus
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Imunidade Inata
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article