title: Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation.
abstract: A key feature differentiating nonpathogenic SIV infection of sooty mangabeys (SMs) from pathogenic HIV/SIV infections is the rapid resolution of type I IFN (IFN-I) responses and IFN-stimulated gene expression during the acute-to-chronic phase transition and the establishment of an immune quiescent state that persists throughout the chronic infection. We hypothesized that low levels of IFN-I signaling may help to prevent chronic immune activation and disease progression in SIV-infected SMs. To assess the effects of IFN-I signaling in this setting, in the present study, we administered recombinant rhesus macaque IFNα2-IgFc (rmIFNα2) to 8 naturally SIV-infected SMs weekly for 16 weeks. Gene-expression profiling revealed a strong up-regulation of IFN-stimulated genes in the blood of treated animals, confirming the reagent's bioactivity. Interestingly, we observed an approximately 1-log decrease in viral load that persisted through day 35 of treatment. Flow cytometric analysis of lymphocytes in the blood, lymph nodes, and rectal biopsies did not reveal a significant decline of CD4(+) T cells, a robust increase in lymphocyte activation, or change in the level of SIV-specific CD8(+) T cells. The results of the present study indicate that administration of type I IFNs in SIV-infected SMs induces a significant anti-viral effect that is not associated with a detectable increase in chronic immune activation.
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Vanderford
authors.forename: Chloe
authors.initials: C
authors.lastname: Slichter
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Rogers
authors.forename: Benton O
authors.initials: BO
authors.lastname: Lawson
authors.forename: Rend
authors.initials: R
authors.lastname: Obaede
authors.forename: James
authors.initials: J
authors.lastname: Else
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016665:Cercocebus atys / Q000097:blood / Q000276:immunology / Q000821:virology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000819:agonists* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008212:Lymphocyte Depletion; D008253:Macaca mulatta / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000097:blood / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins