title: Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers.
abstract: 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.
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France. asier.saez-cirion@pasteur.fr
authors.forename: Asier
authors.initials: A
authors.lastname: Sáez-Cirión
authors.forename: Chiraz
authors.initials: C
authors.lastname: Hamimi
authors.forename: Anna
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Annie
authors.initials: A
authors.lastname: David
authors.forename: Pierre
authors.initials: P
authors.lastname: Versmisse
authors.forename: Adeline
authors.initials: A
authors.lastname: Mélard
authors.forename: Faroudy
authors.initials: F
authors.lastname: Boufassa
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
mesh_terms: D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004198:Disease Susceptibility / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008297:Male; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014779:Virus Replication / Q000502:physiology*
chemical_list: D004279:DNA, Viral; D034741:RNA, Small Interfering