BF Integrase Genes of HIV-1 Circulating in Sao Paulo, Brazil, with a Recurrent Recombination Region

Author(s)

Iamarino, Atila ^[1] ; de Melo, Fernando Lucas ^[1] ; Braconi, Carla Torres ^[1] ; de Andrade Zanotto, Paolo Marinho ^[1]

Affiliation

^[1] Univ Sao Paulo, Lab Mol Evolut & Bioinformat, Dept Microbiol, Biomed Sci Inst ICB 2, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 7, n. 4 APR 2 2012.
• Web of Science Citations: 3

Abstract

Although some studies have shown diversity in HIV integrase (IN) genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naive patients from the Sao Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes), 17 of subtype F (8 of which were found in recombinant genomes), 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2) that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naive and 45% of the drug-treated patients had at least 1 raltegravir (RAL) or elvitegravir (EVG) resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS) indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population. (AU)

• FAPESP's process: 09/16740-8 - Study of structural proteins of Anticarsia gemmatalis nucleopoliedrovirus (AgMNPV-2D) in different insect cell lines and comparison of the GP64 in geographic variants
• Grantee: Carla Torres Braconi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 07/01554-9 - Biological and molecular characterization of HIV-1 natural recombinants
• Grantee: Fernando Lucas de Melo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/19341-4 - Biological characterization of natural and artificial HIV-1 recombinants between subtypes B and F
• Grantee: Paolo Marinho de Andrade Zanotto
• Support Opportunities: Regular Research Grants