title: Downregulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques.
abstract: The mechanisms underlying the AIDS resistance of natural hosts for simian immunodeficiency virus (SIV) remain unknown. Recently, it was proposed that natural SIV hosts avoid disease because their plasmacytoid dendritic cells (pDCs) are intrinsically unable to produce alpha interferon (IFN-alpha) in response to SIV RNA stimulation. However, here we show that (i) acute SIV infections of natural hosts are associated with a rapid and robust type I IFN response in vivo, (ii) pDCs are the principal in vivo producers of IFN-alpha/beta at peak acute infection in lymphatic tissues, and (iii) natural SIV hosts downregulate these responses in early chronic infection. In contrast, persistently high type I IFN responses are observed during pathogenic SIV infection of rhesus macaques.
authors.affiliation: Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Levelle D
authors.initials: LD
authors.lastname: Harris
authors.forename: Brian
authors.initials: B
authors.lastname: Tabb
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Michaela
authors.initials: M
authors.lastname: Müller-Trutwin
authors.forename: Ivona
authors.initials: I
authors.lastname: Vasile-Pandrea
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hirsch
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lifson
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D007370:Interferon Type I