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Prevention of SHIV transmission by topical IFN-β treatment
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Journal Article
Prevention of SHIV transmission by topical IFN-β treatment
2016
Overview
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.
Publisher
Elsevier Inc,Nature Publishing Group US
Subject
/ Administration, Intravaginal
/ Animals
/ Antiviral Agents - administration & dosage
/ Biomedical and Life Sciences
/ Female
/ Gene Expression Regulation - drug effects
/ Interferon-beta - administration & dosage
/ Lymphocyte Activation - immunology
/ Myeloid Cells - drug effects
/ Receptors, CCR5 - metabolism
/ Simian Acquired Immunodeficiency Syndrome - immunology
/ Simian Acquired Immunodeficiency Syndrome - prevention & control
/ Simian Acquired Immunodeficiency Syndrome - transmission
/ Simian Acquired Immunodeficiency Syndrome - virology
/ Simian Immunodeficiency Virus - drug effects
/ Simian Immunodeficiency Virus - immunology
/ T-Lymphocyte Subsets - drug effects
/ T-Lymphocyte Subsets - immunology
