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Epigenetic analysis of genes involved in type I interferon response and functional profile of cells from innate and adaptive immunity in serodiscordant couples for HIV-1

Grant number: 15/00263-7
Support Opportunities:Regular Research Grants
Duration: September 01, 2015 - August 31, 2017
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Maria Notomi Sato
Grantee:Maria Notomi Sato
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


There are some individuals that even after repeated exposure to HIV-1 by the infected partner remain seronegative and are named as HIV-1 exposed uninfected individuals (ENIs). In addition to genetic and virologic factors, the innate immunity factors able to enhance the adaptive function in the ENI, may be associated with the resistance to HIV infection. Among the parameters of innate immunity, the viral restriction factors, antimicrobial as well as the effector function of Natural Killer (NK) cells induced by the activation of Toll-like receptors (TLR), needs further information on ENIs. Similarly, there is scarce evidence on the polyfunctional profile of CD4 + and CD8 + T cells. Moreover, it is not clear whether the epigenetic changes may influence the controlling of innate or adaptive immune response of ENIs. The aim of this study is to evaluate the molecular and epigenetic parameters (methylation degree and microRNAs) related to innate immunity and the adaptive response and the polyfunctional capacity of NK cells and T cells in serodiscordant couples to compare with seroconcordant couples and healthy individuals. To evaluate the innate immunity, the profile of viral restriction factors expression will be assessed in oral epithelial cells and peripheral blood mononuclear cells and the presence of antimicrobial factors and chemokines will be assessed in the oral fluid and serum. In innate immunity approach includes the analysis of the functional response of NK cells from peripheral blood induced by TLR3 activation. As the adaptive response will be evaluated the monofunctional (Th1, Th17, Th22, Tc22) and polyfunctional cytokines production (IL-17, IL-22, IL-2, IFN-³, MIP-1²) and cytotoxicity induced by HIV-1 Gag in CD4+ and CD8+ T cells. The epigenetic question in the NK cells and CD4+ T cells, will be assessed by the methylation of promoter genes of cytokines and IFN type I and II (restriction enzymes and ChiP) and expression of microRNAs involved in the pro/anti-inflammatory response. These data allow us to understand correlates of resistance to HIV-1 and may favor the development of vaccine adjuvant to HIV-1. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OLIVEIRA, LUANDA M. S.; LIMA, JOSENILSON F.; CERVANTES, CESAR A. C.; CASSEB, JORGE S.; MENDONCA, MARCELO; DUARTE, ALBERTO J. S.; SATO, MARIA N.. Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38(-) T cells in HIV-exposed uninfected subjects. SCIENTIFIC REPORTS, v. 5, . (15/00263-7)
LIMA, JOSENILSON F.; OLIVEIRA, LUANDA M. S.; PEREIRA, NATALLI Z.; DUARTE, ALBERTO J. S.; SATO, MARIA N.. Polyfunctional natural killer cells with a low activation profile in response to Toll-like receptor 3 activation in HIV-1-exposed seronegative subjects. SCIENTIFIC REPORTS, v. 7, . (15/00263-7)
CERVANTES, CESAR A. C.; OLIVEIRA, LUANDA M. S.; MANFRERE, KELLY C. G.; LIMA, JOSENILSON F.; PEREIRA, NATALLI Z.; DUARTE, ALBERTO J. S.; SATO, MARIA N.. Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples. SCIENTIFIC REPORTS, v. 6, . (10/15756-5, 15/00263-7)

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