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Study of the diversity of the HIV-1 V3 region in patients in different clinical stages

Grant number: 19/09841-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2019
Effective date (End): June 30, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Shirley Cavalcante Vasconcelos
Grantee:Matheus Borri Marroni
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). The envelope of the virus contains the glycoprotein 120 (gp120) which is formed by five constant regions and five variables, among which is the V3 loop. The V3 loop / region is formed by 35 amino acids being one of the main targets of the immune system and at its top (motif) has an amino acid tetrad that distinguishes the American antigenic variants (GPGR) from Brazilian (GWGR). It is responsible for the tropism of the virus and entry events, moreover, can induce both cellular immune responses: helper T cells and cytotoxic T cells. For these reasons has been studied over the years for the design of vaccines and drugs. Because it is a target of the immune system and also of a drug, the selection of viral variants (quasispecies) with better replication capacity and survival in the host takes place, which leads to the constant generation of diversity. In this project the main objective is to analyze the diversity of HIV-1 V3 region among samples of HIV-positive patients in therapeutic failure to different antiretroviral drug regimens and newly diagnosed. During the study, 100 samples of plasma-purified RNAs from patients infected with HIV-1 will be analyzed through the Polymerase Chain Reaction and Sanger sequencing. To characterize the viral tropism will be used the website Geno2pheno (https://coreceptor.geno2pheno.org/). The sequences will be edited in Sequencher software (Gene Codes Corporation), aligned in the software Bioedit (Clustal X program). The rate of synonymous and non-synonymous substitutions of the C2V3C3 region for selective pressure verification will be performed using the HIV databases tool (https://www.hiv.lanl.gov/content/sequence/SNAP/SNAP.html), among the groups of patients in failed therapy and newly diagnosed HIV + and without treatment with antiretrovirals.