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

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

Abstract

How HIV controllers (HIC) maintain undetectable viremia without therapy is unknown. The strong CD8+ T cell HIV suppressive capacity found in many, but not all, HIC may contribute to long lasting viral control. However, other earlier defence 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 HIC showed low HIV-1 susceptibility. CD4 T cell resistance was independent of HIV-1 coreceptors and affected also SIVmac infection. CD4+ T cells from HIC expressed ex vivo higher levels of p21Waf1/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 to 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 HIC 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 HIC.

  • Submitted December 23, 2010.
  • Accepted May 18, 2011.