Generalized immune activation and innate immune responses in simian immunodeficiency virus infectionBosinger, Steven E.a; Sodora, Donald L.b; Silvestri, GuidoaCurrent Opinion in HIV & AIDS: September 2011 - Volume 6 - Issue 5 - p 411–418 doi: 10.1097/COH.0b013e3283499cf6 Innate immunity: Edited by William A. Paxton and Teunis B.H. Geijtenbeek Abstract Author Information Purpose of review: Chronic immune activation is a key factor driving the immunopathogenesis of AIDS. During pathogenic HIV/simian immunodeficiency virus (SIV) infections, innate and adaptive antiviral immune responses contribute to chronic immune activation. In contrast, nonpathogenic SIV infections of natural hosts such as sooty mangabeys and African green monkeys (AGMs) are characterized by low immune activation despite similarly high viremia. This review focuses on the role of innate immune responses in SIV infection. Recent findings: Several studies have examined the role of innate immune responses to SIV as potential drivers of immune activation. The key result of these studies is that both pathogenic SIV infection of macaques and nonpathogenic SIV infections of natural hosts are associated with strong innate immune responses to the virus, high production of type I interferons by plasmacytoid dendritic cells, and upregulation of interferon-stimulated genes (ISGs). However, SIV-infected sooty mangabeys and AGMs (but not SIV-infected macaques) rapidly downmodulate the interferon response within 4–6 weeks of infection, thus resulting in a state of limited immune activation during chronic infection. Summary: Studies in nonhuman primates suggest that chronic innate/interferon responses may contribute to AIDS pathogenesis. Further, the ability of natural host species to resolve innate immune responses after infection provides a novel avenue for potential immunotherapy. aYerkes National Primate Research Center, and Emory Vaccine Center, Emory University, Atlanta, Georgia bSeattle Biomedical Research Institute, Seattle, Washington, USA Correspondence to Guido Silvestri, MD, Yerkes National Primate Research Center, Emory University School of Medicine, 3014 EVC Building, 954 Gatewood Rd NE, Atlanta, GA 30329, USATel: +1 404 7279139; fax: +1 404 7277768; e-mail: firstname.lastname@example.org © 2011 Lippincott Williams & Wilkins, Inc.