Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response
Béatrice Jacquelin, … , Arndt Benecke, Michaela C. Müller-Trutwin
Béatrice Jacquelin, … , Arndt Benecke, Michaela C. Müller-Trutwin
Published November 23, 2009
Citation Information: J Clin Invest. 2009;119(12):3544-3555. https://doi.org/10.1172/JCI40093.
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Research Article

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

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.

Authors

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

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Figure 5

In vitro induction of type I ISG and IFN-α.

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In vitro induction of type I ISG and IFN-α. Peripheral CD4+ cells of uni...
Peripheral CD4+ cells of uninfected AGMs (blue) and RMs (red) were cultured in the presence of the CD4– cell fraction in a 2-chamber system. (A and B) Cells were incubated for 12, 18, and 24 hours with SIV or 1,500 IU/ml of human recombinant IFN-α. Viral infectious titers used are indicated. (C and D) Cells were incubated with a range of doses of recombinant IFN-α. (A and C) For MX1 gene expression, the mean ± SEM of log2Q is shown. (B and D) Means of the amounts of bioactive IFN-α produced in supernatants are represented (±SEM). The means were calculated from 3 independent experiments with cells from 3 different animals of each species.