Modulation of Type I Interferon-Associated Viral Sensing during Acute Simian Immunodeficiency Virus Infection in African Green Monkeys

Natural hosts of simian immunodeficiency virus (SIV), such asAfrican greenmonkeys (AGMs), do not progress toAIDSwhen infected with SIV. This is associatedwith an absence of a chronic type I interferon (IFN-I) signature. It is unclear how the IFN-I response is downmodulated inAGMs.We longitudinally assessed the capacity of AGMblood cells to produce IFN-I in response to SIV andherpes simplex virus (HSV) infection. Phenotypes and functions of plasmacytoid dendritic cells (pDCs) and othermononuclear blood cells were assessed by flow cytometry, and expression of viral sensorswasmeasured by reverse transcription-PCR. pDCs displayed low BDCA-2, CD40, andHLA-DR expression levels duringAGMacute SIV (SIVagm) infection. BDCA-2was required for sensing of SIV, but not ofHSV, by pDCs. In acute infection, AGMperipheral bloodmononuclear cells (PBMCs) produced less IFN-I upon SIV stimu-lation. In the chronic phase, the productionwas normal, confirming that the lack of chronic inflammation is not due to a sensing defect of pDCs. In contrast to stimulation by SIV,more IFN-Iwas produced uponHSV stimulation of PBMCs isolated during acute infection, while the frequency of AGMpDCs producing IFN-I upon in vitro stimulationwithHSVwas diminished. Indeed, other cells started producing IFN-I. This increased viral sensing by non-pDCswas associatedwith anupregulation of Toll-like receptor 3 and IFN--inducible protein 16 caused by IFN-I in acute SIVagm infection.Our results suggest that, as in pathogenic SIVmac infection, SIVagm infectionmobilizes bonemarrowprecursor pDCs.Moreover, we show that SIV infectionmodifies the capacity of viral sensing in cells other than pDCs,which could drive IFN-I production in specific settings