Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response

Béatrice Jacquelin, Véronique Mayau, Brice Targat, Anne Sophie Liovat, Désirée Kunkel, Gaël Petitjean, Marie Agnès Dillies, Pierre Roques, Cécile Butor, Guido Silvestri, Luis D. Giavedoni, Pierre Lebon, Françoise Barré-Sinoussi, Arndt Benecke, Michaela C. Müller-Trutwin

    Research output: Contribution to journalArticlepeer-review

    335 Scopus citations

    Abstract

    African green monkeys (AGMs) infected with the AGM type of SIV (SIVagm) do not develop chronic immune activation and AIDS, despite viral loads similar to those detected in humans infected with HIV-1 and rhesus macaques (RMs) infected with the RM type of SIV (SIVmac). Because chronic immune activation drives progressive CD4+ T cell depletion and immune cell dysfunctions, factors that characterize disease progression, we sought to understand the molecular basis of this AGM phenotype. To this end, we longitudinally assessed the gene expression profiles of blood- and lymph node-derived CD4+ cells from AGMs and RMs in response to SIVagm and SIVmac infection, respectively, using a genomic microarray platform. The molecular signature of acute infection was characterized, in both species, by strong upregulation of type I IFN-stimulated genes (ISGs). ISG expression returned to basal levels after postinfection day 28 in AGMs but was sustained in RMs, especially in the lymph node-derived cells. We also found that SIVagm induced IFN-α production by AGM cells in vitro and that low IFN-α levels were sufficient to induce strong ISG responses. In conclusion, SIV infection triggered a rapid and strong IFN-α response in vivo in both AGMs and RMs, with this response being efficiently controlled only in AGMs, possibly as a result of active regulatory mechanisms.

    Original languageEnglish (US)
    Pages (from-to)3544-3555
    Number of pages12
    JournalJournal of Clinical Investigation
    Volume119
    Issue number12
    DOIs
    StatePublished - Dec 1 2009

    ASJC Scopus subject areas

    • Medicine(all)

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