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Biological and molecular characterization of HIV-1: identification of epitopes relevant to viral tropism and infection control

Abstract

The adequate use of antiretroviral therapies by people living with HIV/AIDS is a strategic question in Public Health, essential to the control of the epidemic. Among the innovations in the area of antiretroviral medications there are agents that inhibit the binding of the virus to CCR5 co-receptors in host cells, one of the two major viral co-receptors , The efficacy of these medications depend on usage of this co receptor and the drug does not block virus that use alternative co-receptors, as CXCR4. Variants that use the alternative co receptors CXCR4 are more aggressive and are associated to clinical progression. The determination of viral tropism has therefore implications in the understanding of viral pathogenesis, in the epidemiological surveillance and is necessary to subsidize the clinical decision in the use of these antiretrovirals. Albeit the fact that tropism is a biological characteristic defined by differential cell permissively, viral tropism has been predicted by the genotypic analysis of regions of HIV-1 envelope and different bioinformatics tools have helped in this goal. The specificity and especially the sensitivity to detect CXCR4 or duotropic strains have limited its applicability. This project will perform partial molecular characterization of HIV-1 isolates from 270 volunteers in clinical follow up in public services aiming to improve the genotypic prediction of viral tropism, evaluating the available tools in isolates obtained in the country. These tools, usually applied to plasma virions, will be also evaluated in isolates obtained in other biological compartments, as cellular subpopulations . The study will also evaluate markers of clinical progression including the deletion 32 of the CCR5 gene and serum levels of CCR5 ligants as potential markers in viral tropism determination algorithms and to better understand the role of cell tropism in pathogenesis. The data generated will also be evaluated in mathematical models to improve the association of clinical and laboratorial markers as ancillary tools to tropism prediction. The initiative favors the implementation of infrastructure at IAL as well as technical/operational capability to support the Sao Paulo State Secretary of Health .The project has the participation of various groups of the BioMedical Division of the IAL and clinical groups at public services and the state DST-Aids program. (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)
DE PAULA FERREIRA, JOAO LEANDRO; OZORIO COELHO, LUANA PORTES; RODRIGUES, ROSANGELA; CABRAL, GABRIELA BASTOS; CAVALCANTI, JAQUELINE DE SOUZA; DE SOUZA GUIMARAES, PAULA MORENA; DE MACEDO BRIGIDO, LUIS FERNANDO. Evaluation of genotypic prediction of HIV-1 tropism using population sequencing of replicates. Journal of Virological Methods, v. 179, n. 2, p. 325-329, . (09/08215-0)
OZORIO COELHO, LUANA PORTES; DE PAULA FERREIRA, JOAO LEANDRO; CABRAL, GABRIELA BASTOS; DE SOUZA GUIMARAES, PAULA MORENA; DE MACEDO BRIGIDO, LUIS FERNANDO. Genotypic Tropism Prediction from Paired Cell and Plasma Using Single and Replicate Sequences. AIDS Research and Human Retroviruses, v. 30, n. 7, p. 711-716, . (09/08215-0, 11/21958-2)

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