Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study

Author(s)

Pessoa, Rodrigo ^[1] ; Sabino, Ester C. ; Sanabani, Sabri S. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med, Hosp Clin, Dept Pathol, Sao Paulo - Brazil

^[2] Med Inst Med Trop Sao Paulo, BR-05403000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: VIROLOGY JOURNAL; v. 12, MAY 14 2015.
• Web of Science Citations: 2

Abstract

Background: The interaction of HIV-1 and target cells involves sequential binding of the viral gp120 Env protein to the CD4 receptor and a chemokine co-receptor (either CCR5 or CXCR4). CCR5 antagonists have proved to be an effective salvage therapy in patients with CCR5 using variants (R5) but not with variants capable of using CXCR4 (x4) phenotype. Thus, it is critically important to determine cellular tropism of a country's circulating HIV strains to guide a management decision to improve treatment outcome. In this study, we report the prevalence of R5 and x4 HIV strains in 45 proviral DNA massively parallel sequencing ``MPS{''} data from recently infected Brazilian blood donors. Methods: The MPS data encompassing the tropism-related V3 loop region of the HIV-1 env gene was extracted from our recently published HIV-1 genomes sequenced by a paired-end protocol (Illumina). HIV-1 tropism was inferred using Geno2pheno({[}coreceptor]) algorithm (3.5 % false-positive rate). V3 net charge and 11/25 rules were also used for coreceptor prediction. Results: Among the 45 samples for which tropism were determined, 39 were exclusively R5 variants, 5 x4 variants, and one dual-tropic or mixed (D/M) populations of R5 and x4 viruses, corresponding to 86.7, 11.1 and 2.2 %, respectively. Thus, the proportion of all blood donors that harbor CXCR4-using virus was 13.3 % including individuals with D/M-tropic viruses. Conclusions: The presence of CCR5-tropic variants in more than 85 % of our cohort of antiretroviral-naive blood donors with recent HIV-1 infection indicates a potential benefit of CCR5 antagonists as a therapeutic option in Brazil. Therefore, determination of viral co-receptor tropism is an important diagnostic prerequisite. (AU)

• FAPESP's process: 11/11090-5 - Complete genomes for HIV: viral genetic diversity among seropositive first-time blood donors in four blood centres in Brazil
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/24596-2 - HIV 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
• Grantee: Rodrigo Pessoa de Farias
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/12297-2 - Profiling the human T-cells miRNA, REX and tax transcriptomes in the course of HTLV-1 infection using a deep sequencing approach
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support Opportunities: Regular Research Grants