: Molecular and geographic characterization of hiv-1 bf recombinant viruses

Abstract

The Human Immunodeficiency Virus Type 1 (HIV-1) presents a wide genetic variability, which is represented by four groups, nine subtypes of group M and several ACCEPTED MANUSCRIPT 2 recombinant forms. Among these, the BF recombinants have been distinguished by a high global dispersion and an increase in number and diversity. To date, 15 BF Circulating Recombinant Forms (CRFs) and diverse BF Unique Recombinant Forms (URFs) have been described. In Brazil, nine CRF_BF have been identified. The aim of this work was to perform molecular and geographic characterization of HIV-1 BF recombinant strains. Near full-length genomes of 265 BF recombinant viruses were collected from public databases and molecular analyses were performed. These sequences were originally retrieved between 1993-2006 and isolated from 16 countries (51.3% from Brazil). Diagnostic's year analysis showed that BF recombinants circulate in Brazil since at least 1985. Most sequences displayed recombination in the pol (84.9%), gag (69.3%) and env (51.4%) regions. The subtype B predominated in all accessory and regulatory genes, except in vif, in which the F subtype was predominant (40.4%). Twelve regions with a recombination rate higher than 10% were identified, especially one region inside p24 gene (1359-1397) whose recombination was present in more than 30% of the sequences. Coreceptor usage prediction during viral entry showed that BF recombinants preferentially use CCR5 (67.2%) and the most frequent tetrapeptides found in the V3 loop were GPGR (47.9%) and GPGQ (21.1%). The frequency of X4/dual viruses was lower amongst F subtype (25.8%) V3 sequences,compared with B subtype (43%). In addition, mutations associated with intermediate or high resistance levels to PI (10.6%), NRTI (15.0%), NNRTI (14.0%) and INSTI (2.6%) were identified. The great diversity of the recombination patterns evidences that the recombination between the subtypes B and F is frequent, reflecting a probable high rate of dual infection and the acquisition of advantageous characteristics for viral fitness.