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Genetic characterization of an isolate of HIV type 1 AG recombinant form circulating in Siberia, Russia.

ABSTRACT: Before 2008, HIV-1 subtype A was the predominant genetic variant in the Novosibirsk oblast of Russia as well as in most parts of this country. However, a rapid spread of the recombinant HIV-1 02_AG form has been reported in Novosibirsk since 2009. We have analyzed the genome of the 10.RU.6637 isolate, a HIV-1 02_AG recombinant form, which represents a monophyletic cluster of the HIV-1 variants widespread in this region. Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan. However, recombination analysis of 10.RU.6637 has demonstrated that this isolate is a recombinant form between HIV-1 subtype A and CRF02_AG, differing in its genetic structure from both the CRF02_AG reference sequences and the Central Asian variants of HIV-1 02_AG.

SUBMITTER: Baryshev PB

PROVIDER: S-EPMC3506197 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: HIV 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. METHODS: Initially, 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 analysis RESULTS: Of 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. CONCLUSION: We 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.

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Genetic characterization of an isolate of HIV type 1 AG recombinant form circulating in Siberia, Russia.

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