Characterization and frequency of a newly identified HIV-1 BF1 intersubtype circulating recombinant form in São Paulo, Brazil

Abstract

BackgroundHIV circulating recombinant forms (CRFs) play an important role in the global and regional HIV epidemics, particularly in regions where multiple subtypes are circulating. To date, several (>40) CRFs are recognized worldwide with five currently circulating in Brazil. Here, we report the characterization of near full-length genome sequences (NFLG) of six phylogenetically related HIV-1 BF1 intersubtype recombinants (five from this study and one from other published sequences) representing CRF46_BF1.MethodsInitially, we selected 36 samples from 888 adult patients residing in São Paulo who had previously been diagnosed as being infected with subclade F1 based on pol subgenomic fragment sequencing. Proviral DNA integrated in peripheral blood mononuclear cells (PBMC) was amplified from the purified genomic DNA of all 36-blood samples by five overlapping PCR fragments followed by direct sequencing. Sequence data were obtained from the five fragments that showed identical genomic structure and phylogenetic trees were constructed and compared with previously published sequences. Genuine subclade F1 sequences and any other sequences that exhibited unique mosaic structures were omitted from further analysisResultsOf the 36 samples analyzed, only six sequences, inferred from the pol region as subclade F1, displayed BF1 identical mosaic genomes with a single intersubtype breakpoint identified at the nef-U3 overlap (HXB2 position 9347-9365; LTR region). Five of these isolates formed a rigid cluster in phylogentic trees from different subclade F1 fragment regions, which we can now designate as CRF46_BF1. According to our estimate, the new CRF accounts for 0.56% of the HIV-1 circulating strains in São Paulo. Comparison with previously published sequences revealed an additional five isolates that share an identical mosaic structure with those reported in our study. Despite sharing a similar recombinant structure, only one sequence appeared to originate from the same CRF46_BF1 ancestor.ConclusionWe identified a new circulating recombinant form with a single intersubtype breakpoint identified at the nef-LTR U3 overlap and designated CRF46_BF1. Given the biological importance of the LTR U3 region, intersubtype recombination in this region could play an important role in HIV evolution with critical consequences for the development of efficient genetic vaccines.

Short Communication: HIV Type 1 Subtype BF Leads to Faster CD4+ T Cell Loss Compared to Subtype B

“…In this country, five distinct BF CRFs have been described to date (CRF28_BF, CRF29_BF, CRF39_BF, CRF40_BF, and CRF46_BF). 6 By the year of 2006, 62% of AIDS cases reported in Brazil were confined to the Southeast region, with 70% of these cases from Sã o Paulo, the most populous Brazilian city. Interestingly, up to 11% of the HIV-1 isolated in Sã o Paulo to date has shown a mosaic B/F genome.…”

“…[4][5][6][7] Brazil has the highest number of people living with HIV-1 in the region (estimates from 460,000 to 810,000) 8 …”

Characterization of Primary Isolates of HIV Type 1 CRF28_BF, CRF29_BF, and Unique BF Recombinants Circulating in São Paulo, Brazil

“…This could be the case of isolate 0632SV, which may be a new CRF_BF circulating in Sã o Paulo State, since it shares all the recombination breakpoints with a previously published sequence from a nearby location. 49 Most previous in silico analyses characterizing HIV recombinants have been done with bootscanning methods. Even though this methodology is efficient in recombination detection, it is largely dependent on the choice of parental strains, which affect the accuracy of the breakpoint prediction.…”

Molecular Epidemiology of HIV-1 Infection in the Amazon Region

“…In addition to the CRF, a large number of unique recombinant forms (URFs) have been characterized worldwide (McCutchan, 2006). Notoriously, a recombination is a potentially important mechanism that significantly contributes to HIV genetic variability with serious implications for diagnosis, drug treatment and optimal vaccine development (Sanabani et al, 2010).…”