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

Asier Saez-Cirion (1) , Chiraz Hamimi (1) , Anna Bergamaschi (1) , Annie David (1) , Pierre Versmisse (1) , Adeline Mélard (2) , Faroudy Boufassa (3) , Françoise Barré-Sinoussi (1) , Olivier Lambotte (4, 5) , Christine Rouzioux (6, 2) , Gianfranco Pancino (1) , Anrs Co18 Cohort

1 Régulation des Infections Rétrovirales
2 Laboratoire de Virologie [CHU Necker]
3 CESP - Centre de recherche en épidémiologie et santé des populations
4 INSERM U1012
5 Service de médecine interne et maladies infectieuses
6 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine

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.

Mots clés: Macrophages; Male; Blotting; Western; CD4-Positive T-Lymphocytes; Disease Susceptibility; DNA; Viral; Female; HIV-1; HIV Infections; Humans; RNA; Small Interfering; Transfection; Virus Replication; Reverse Transcriptase Polymerase Chain Reaction

Domaines: Immunologie

Asier Saez-Cirion, Chiraz Hamimi, Anna Bergamaschi, Annie David, Pierre Versmisse, et al.. Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers. Blood, 2011, 118 (4), pp.955--964. ⟨10.1182/blood-2010-12-327106⟩. ⟨pasteur-01420583⟩