HIV-1 massively parallel sequencing data in plasma and peripheral blood mononuclear cells from untreated blood donors: Comparison of the near full-length genome subtypes, drug resistance mutations and co-receptor usage

• Grant number: 14/26983-3
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2015
• End date: October 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ester Cerdeira Sabino

Abstract

HIV-1 infection is known to exhibit tremendous genetic variation. Even within a single subject, the virus exists as a swarm of highly related but genetically diverse variants. Although much of these variations are derived from mutations introduced by the error prone reverse transcriptase, viral recombination contributes significantly in genetic evolution as well. In clinical practice, the viral genotypic and tropism features are commonly defined on plasma RNA as representative of the viral population by standard bulk-sequencing but this assay may not detect minority variants. Massively parallel sequencing (MPS) detects single clones thereby being much more sensitive. It is obvious that retrieving HIV drug resistance mutations (DRMs) and defining coreceptor usage in sequences from cell-associated viruses may be easier and less expensive than in plasma RNA viruses, but their clinical significance in proviral DNA is still not less clear. As a result, comparative studies of plasma and PBMC viral population are needed to address this potential shift in sample type selection. In our last study, we were able to generate the MPS of HIV-1 proviral near-full length genomes (NFLG) from 270 blood donors' samples. In the current project, we aimed to further explore our last findings by generating HIV-1 NFLG MPS data from 70 plasma samples of the last group and compare the plasma viral population against the PBMC population in terms of viral genetic diversities, drug resistance mutations and coreceptor usage. To this end, viral RNA will be extracted and converted to double stranded DNA. Consequently, the dsDNA will directly be fragmented, molecularly bar-coded, pooled, and sequenced by Illumina paired-end protocol (detailed information and pilot results are enclosed in the project). Results from this study are expected to enhance our standing of the HIV-1 evolution within hosts and address whether PBMC and plasma hosted drastically different viral variants and what the implications of these variants in predict treatment outcomes and coreceptor usage. (AU)

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)

PEREIRA DA FONSECA, TAIRACAN AUGUSTO; PESSOA, RODRIGO; SANABANI, SABRI SAEED. Molecular investigation of bacterial communities: Data from two frequently used surfaces in the Sao Paulo Institute of Tropical Medicine. DATA IN BRIEF, v. 8, p. 399-403, SEP 2016. (14/26983-3, 11/12297-2)

PESSOA, RODRIGO; SANABANI, SABRI S.. High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naive chronically infected Brazilian blood donors. PLoS One, v. 12, n. 9, SEP 27 2017. (14/26983-3, 14/24596-2)

PEREIRA DA FONSECA, TAIRACAN AUGUSTO; PESSOA, RODRIGO; FELIX, ALVINA CLARA; SANABANI, SABRI SAEED. Diversity of Bacterial Communities on Four Frequently Used Surfaces in a Large Brazilian Teaching Hospital. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, v. 13, n. 2, FEB 2016. (14/26983-3, 11/12297-2)