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.

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

“…African green monkeys, which are considered to be the natural host of SIVagm, will not progress to AIDS even though they show high viral loads upon SIV infection. Jacquelin et al 27 reported a strong type I IFN response in the acute phase of infection in the African green monkey, but immune activation was controlled during chronic infection, a response that differed from that of the rhesus macaques. In addition, our study also showed that pDC activation is highly correlated with disease pathogenesis in SIVmac239 infection, as the macaques in the late phase of infection had higher pDC activation compared with the chronic infected macaques.…”

Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

“…However, there are major differences compared with SIVmac infection in macaques: the levels of several cytokines, including IFN-a, are lower than those observed during acute SIVmac infection, which is not due to a functional defect in the ability of pDCs to sense the virus [188,189]. Indeed, the TLR7/TLR9/IRF7 pathway is functional [188,189].…”

“…Indeed, the TLR7/TLR9/IRF7 pathway is functional [188,189]. In addition, natural hosts preserve their TH17 cells, and their epithelial barriers are not damaged and consequently they show no signs of microbial translocation.…”

Se protéger du SIDA ?

“…Au contraire, chez l'AGM infecté par le SIVagm, la production de ces cytokines est globalement modérée [6]. Toutefois, une augmentation significative d'IFN-est observée dans les premières semaines de l'infection [8,9]. L'activité biologique des interférons se traduit par l'induction de l'expression de gènes appelés ISG pour IFN stimulated genes.…”

“…L'activité biologique des interférons se traduit par l'induction de l'expression de gènes appelés ISG pour IFN stimulated genes. Nous avons récemment montré que les ISG sont fortement induits et de manière identique pendant la phase aiguë de l'infection SIV chez l'AGM et chez le macaque (Figure 1D) [9]. Mais, alors que l'expression de ces gènes reste élevée dans les cellules du sang et des ganglions lymphatiques chez le macaque, elle décroît jusqu'à son niveau basal chez l'AGM dès la fin de la phase aiguë (4 semaines post-infection).…”