title: Prevention of SHIV transmission by topical IFN-β treatment.
abstract: Understanding vaginal and rectal HIV transmission and protective cellular and molecular mechanisms is critical for designing new prevention strategies, including those required for an effective vaccine. The determinants of protection against HIV infection are, however, poorly understood. Increasing evidence suggest that innate immune defenses may help protect mucosal surfaces from HIV transmission in highly exposed, uninfected subjects. More recent studies suggest that systemically administered type 1 interferon protects against simian immunodeficiency virus infection of macaques. Here we hypothesized that topically applied type 1 interferons might stimulate vaginal innate responses that could protect against HIV transmission. We therefore applied a recombinant human type 1 interferon (IFN-β) to the vagina of rhesus macaques and vaginally challenged them with pathogenic simian/human immunodeficiency virus (SHIV). Vaginal administration of IFN-β resulted in marked local changes in immune cell phenotype, increasing immune activation and HIV co-receptor expression, yet provided significant protection from SHIV acquisition as interferon response genes were also upregulated. These data suggest that protection from vaginal HIV acquisition may be achieved by activating innate mucosal defenses.
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University/University Hospitals/Case Medical Center, Cleveland, Ohio, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Pilch-Cooper
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Hope
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: G
authors.initials: G
authors.lastname: Alter
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Carias
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Sips
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University/University Hospitals/Case Medical Center, Cleveland, Ohio, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University/University Hospitals/Case Medical Center, Cleveland, Ohio, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Sieg
authors.affiliation: The Scripps Research Institute Florida, Jupiter, Florida, USA.
authors.forename: A
authors.initials: A
authors.lastname: Reich
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University/University Hospitals/Case Medical Center, Cleveland, Ohio, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wilkinson
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cameron
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University/University Hospitals/Case Medical Center, Cleveland, Ohio, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000282:Administration, Intravaginal; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers; D015704:CD4 Antigens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016899:Interferon-beta / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000821:virology; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D015704:CD4 Antigens; D019713:Receptors, CCR5; D016899:Interferon-beta
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