title: Modulation of type I interferon-associated viral sensing during acute simian immunodeficiency virus infection in African green monkeys.
abstract: Natural hosts of simian immunodeficiency virus (SIV), such as African green monkeys (AGMs), do not progress to AIDS when infected with SIV. This is associated with an absence of a chronic type I interferon (IFN-I) signature. It is unclear how the IFN-I response is downmodulated in AGMs. We longitudinally assessed the capacity of AGM blood cells to produce IFN-I in response to SIV and herpes simplex virus (HSV) infection. Phenotypes and functions of plasmacytoid dendritic cells (pDCs) and other mononuclear blood cells were assessed by flow cytometry, and expression of viral sensors was measured by reverse transcription-PCR. pDCs displayed low BDCA-2, CD40, and HLA-DR expression levels during AGM acute SIV (SIVagm) infection. BDCA-2 was required for sensing of SIV, but not of HSV, by pDCs. In acute infection, AGM peripheral blood mononuclear cells (PBMCs) produced less IFN-I upon SIV stimulation. In the chronic phase, the production was 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-I was produced upon HSV stimulation of PBMCs isolated during acute infection, while the frequency of AGM pDCs producing IFN-I upon in vitro stimulation with HSV was diminished. Indeed, other cells started producing IFN-I. This increased viral sensing by non-pDCs was associated with an upregulation of Toll-like receptor 3 and IFN-γ-inducible protein 16 caused by IFN-I in acute SIVagm infection. Our results suggest that, as in pathogenic SIVmac infection, SIVagm infection mobilizes bone marrow precursor pDCs. Moreover, we show that SIV infection modifies the capacity of viral sensing in cells other than pDCs, which could drive IFN-I production in specific settings.
  
  
  OBJECTIVE
  The effects of HIV/SIV infections on the capacity of plasmacytoid dendritic cells (pDCs) to produce IFN-I in vivo are still incompletely defined. As IFN-I can restrict viral replication, contribute to inflammation, and influence immune responses, alteration of this capacity could impact the viral reservoir size. We observed that even in nonpathogenic SIV infection, the frequency of pDCs capable of efficiently sensing SIV and producing IFN-I was reduced during acute infection. We discovered that, concomitantly, cells other than pDCs had increased abilities for viral sensing. Our results suggest that pDC-produced IFN-I upregulates viral sensors in bystander cells, the latter gaining the capacity to produce IFN-I. These results indicate that in certain settings, cells other than pDCs can drive IFN-I-associated inflammation in SIV infection. This has important implications for the understanding of persistent inflammation and the establishment of viral reservoirs.
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Jochems
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Petitjean
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Désirée
authors.initials: D
authors.lastname: Kunkel
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Liovat
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Mickaël J
authors.initials: MJ
authors.lastname: Ploquin
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.affiliation: Laboratoire de Virologie, Hôpital Saint-Vincent de Paul, and Université Paris Descartes, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Jacquelin
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France michaela.muller-trutwin@pasteur.fr.
authors.forename: Michaela C
authors.initials: MC
authors.lastname: Müller-Trutwin
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D007370:Interferon Type I / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D007370:Interferon Type I