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Expression of antiviral factors and endogenous retroviruses constitutive and induced by agonists of toll-like receptors in HIV-1 infected mothers and newborns

Grant number: 12/21364-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2014
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Maria Notomi Sato
Grantee:Nátalli Zanete Pereira
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Vertical transmission of HIV occurs in a small percentage of children, with 65-80% of newborns do not become infected even in the absence of antiretroviral therapy. This protection combined with immunological immaturity of newborn makes the study of maternal-fetal interaction a great opportunity to understand the factors that are associated with immune protection of newborns, even during treatment antiretroviral. A project proposal is evaluating the innate immunity of mothers infected with HIV-1 and their newborns, the expression of antiviral factors APOBEC3G and TRIM-5± type I IFN and the immunomodulatory potential of agonists of Toll-like receptors (TLR) in the expression of factors. Also assess the influence of the expression of endogenous retroviruses (HERV-K) in the expression of antiviral factors. To this end, we will analyze the transcriptional expression of APOBEC3G, TRIM-5± and type I IFN and viral factors, HIV Gag and Gag of HERV-K in mononuclear cells from peripheral blood (PBMC) of the mother and the cord and after stimulation with agonists of TLR3, TLR7 and TLR7/8. Parallel, protein expression of APOBEC3G and Gag HIV and HERV-K will be evaluated in PBMCs and after ex vivo activation via TLR7/8. A protein and transcriptional expression of antiviral factors and of HERV-K will also be analyzed in placental tissue. The frequency of CD4 + and CD8 + naive, central memory and peripheral will be assessed for expression of APOBEC3G, IFN-g, TNF-a and MIP-1 an induced by agonist of TLR7 / 8 and Gag HERV-K and HIV-1. The understanding of the innate immune response, with emphasis on antiviral factors and endogenous retrovirus and its modulation by ligands for TLRs, can promote possible correlates of protection and provide grants to develop new formulations of HIV vaccines. (AU)