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Interaction between HIV and bone metabolism and dependence on extracellular vesicles and inflammatory cytokines

Grant number: 15/12965-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): November 01, 2015
Effective date (End): October 31, 2016
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Anderson Marliere Navarro
Grantee:Erika Grasiela Marques de Menezes
Supervisor abroad: Philip Norris
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Blood Systems Research Institute (BSRI), United States  
Associated to the scholarship:13/10765-4 - Influence of inflammatory markers of bone metabolism of HIV-seropositive patients in use or not antiretroviral therapy, BP.DR


HIV causes inflammatory immune responses that induces the exhaustion of CD4+ T cells. We hypothesize that not only does HIV use the vesiculation pathway for its assembly and dissemination, but also exploits the transfer of extracellular vesicles to mediate immune signaling. Extracellular vesicles express different markers on their surface, depending on the cells from which they originate, including bone-forming cells. These vesicles may contain RNA, lipids, and proteins, providing valuable information about the health status of the cell of origin. Therefore, we will work with the interaction between HIV and bone metabolism and the involvement of extracellular vesicles and pro-inflammatory cytokines to better understand the HIV-mediated molecular mechanisms in bone cells. Objective: To evaluate the concentration of extracellular vesicles, particularly those derived from osteoclasts in HIV-seropositive subjects with or without osteopenia and in HIV-negative healthy subjects. Methods: A cross-sectional study will be conducted on 60 adult women, aged between 18 and 40. Study participants will be subdivided in three groups, HIV+ women on successful antiretroviral therapy (ART, HIV RNA level <50 copies/ml) with osteopenia (n=20) or with normal bone mineral density group (n=20) and HIV-negative healthy control subjects (n=20). Cryopreserved plasma samples will be tested to determine the concentrations of extracellular vesicles using the fluorochrome-conjugated monoclonal antibodies, including CD41a-PerCP/Cy5.5 (platelet markers), CD3-PerCP/Cy5.5, CD19-Alexa/700 (T and B cell markers), CD14-APC/Cy7 (monocyte marker), CD254/biotin (RANK ligand), and annexin V-PE (bone cell markers). Plasma levels of IL-17 and tumor necrosis factor-± (TNF-±) will be assayed using the standard-sensitivity Milliplex Luminex assay. Statistical tests will be performed to test for equality between groups. Analysis of variance will be used to identify significant differences among groups, using an appropriate post-test. Correlations between quantitative variables will be assessed by linear regression. For the analysis values will be considered significant when p<0.05, and correction for multiple comparisons will be performed.

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)
DE MENEZES, ERIKA G. MARQUES; RAMALLHO, JANAINA; BUCOVSKY, MARIANA; SHANE, ELIZABETH; YIN, MICHAEL T.; NORRIS, PHILIP J. Serum extracellular vesicles expressing bone activity markers associate with bone loss after HIV antiretroviral therapy. AIDS, v. 34, n. 3, p. 351-361, MAR 1 2020. Web of Science Citations: 0.

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