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Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers

2011; Elsevier BV; Volume: 118; Issue: 4 Linguagem: Inglês

10.1182/blood-2010-12-327106

1528-0020

Asier Sáez‐Cirión, Chiraz Hamimi, Anna Bergamaschi, Annie David, Pierre Versmisse, Adeline Mélard, Faroudy Boufassa, Françoise Barré‐Sinoussi, Olivier Lambotte, Christine Rouzioux, Gianfranco Pancino,

Immune Cell Function and Interaction

How HIV controllers (HICs) maintain undetectable viremia without therapy is unknown. The strong CD8(+) T-cell HIV suppressive capacity found in many, but not all, HICs may contribute to long-lasting viral control. However, other earlier defense mechanisms may be involved. Here, we examined intrinsic HIC cell resistance to HIV-1 infection. After in vitro challenge, monocyte-derived macrophages and anti-CD3-activated CD4(+) T cells from HICs showed low HIV-1 susceptibility. CD4 T-cell resistance was independent of HIV-1 coreceptors and affected also SIVmac infection. CD4(+) T cells from HICs expressed ex vivo higher levels of p21(Waf1/Cip1), which has been involved in the control of HIV-1 replication, than cells from control subjects. However, HIV restriction in anti-CD3-activated CD4(+) T cells and macrophages was not associated with p21 expression. Restriction inhibited accumulation of reverse transcripts, leading to reduction of HIV-1 integrated proviruses. The block could be overcome by high viral inocula, suggesting the action of a saturable mechanism. Importantly, cell-associated HIV-1 DNA load was extremely low in HICs and correlated with CD4(+) T-cell permissiveness to infection. These results point to a contribution of intrinsic cell resistance to the control of infection and the containment of viral reservoir in HICs.