<i>Short Communication:</i>Molecular Characterization of HIV Type 1 BF Pol Recombinants from São Paulo, Brazil

Souza, Ana Carolina Mamana Fernandes de; Oliveira, Cristina Mendes de; Rodrigues, Célia Luiza de Lima; Silva, Synara Alexandre Araújo; Levi, José Eduardo

doi:10.1089/aid.2008.0089

Cited by 15 publications

(7 citation statements)

References 25 publications

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“…The result of the phylogenetic analyses, which agreed with previous publications [40,49,50] and thus not shown here, demonstrated that B and F fragments of the jpHMM-confirmed CRF12, CRF28, and CRF29 were inter-mingled, and therefore could not support a single direction of HIV-1 flow. Also, as already mentioned, we found that Argentinean B and F sequence fragments in the HIV database can cover a full HIV-1 genome of each subtype, meaning that there was a potential to form any BF recombinants in Argentina and that there was no need to assume that already-recombined genomes came from Brazil.…”

Section: Resultssupporting

confidence: 90%

The role of recombination in the emergence of a complex and dynamic HIV epidemic

Zhang

Foley

Schultz³

et al. 2010

Retrovirology

119

121

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BackgroundInter-subtype recombinants dominate the HIV epidemics in three geographical regions. To better understand the role of HIV recombinants in shaping the current HIV epidemic, we here present the results of a large-scale subtyping analysis of 9435 HIV-1 sequences that involve subtypes A, B, C, G, F and the epidemiologically important recombinants derived from three continents.ResultsThe circulating recombinant form CRF02_AG, common in West Central Africa, appears to result from recombination events that occurred early in the divergence between subtypes A and G, followed by additional recent recombination events that contribute to the breakpoint pattern defining the current recombinant lineage. This finding also corrects a recent claim that G is a recombinant and a descendant of CRF02, which was suggested to be a pure subtype. The BC and BF recombinants in China and South America, respectively, are derived from recent recombination between contemporary parental lineages. Shared breakpoints in South America BF recombinants indicate that the HIV-1 epidemics in Argentina and Brazil are not independent. Therefore, the contemporary HIV-1 epidemic has recombinant lineages of both ancient and more recent origins.ConclusionsTaken together, we show that these recombinant lineages, which are highly prevalent in the current HIV epidemic, are a mixture of ancient and recent recombination. The HIV pandemic is moving towards having increasing complexity and higher prevalence of recombinant forms, sometimes existing as "families" of related forms. We find that the classification of some CRF designations need to be revised as a consequence of (1) an estimated > 5% error in the original subtype assignments deposited in the Los Alamos sequence database; (2) an increasing number of CRFs are defined while they do not readily fit into groupings for molecular epidemiology and vaccine design; and (3) a dynamic HIV epidemic context.

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Section: Resultssupporting

confidence: 90%

The role of recombination in the emergence of a complex and dynamic HIV epidemic

Zhang

Foley

Schultz³

et al. 2010

Retrovirology

119

121

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“…Subtype C, F1, CRF31 BC and CRF02_AG were detected in small proportions. Overall, these data demonstrate a mature heterogeneous epidemic, which is consistent with the results of previous epidemiological studies in Brazil [29], [30], [31], [32], [33], [34]. In the phylogenetic analysis of NFLGs, there was evidence of various clusters of non-recombinant subtype B sequences.…”

Section: Discussionsupporting

confidence: 91%

Characterization of Partial and Near Full-Length Genomes of HIV-1 Strains Sampled from Recently Infected Individuals in São Paulo, Brazil

et al. 2011

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BackgroundGenetic variability is a major feature of human immunodeficiency virus type 1 (HIV-1) and is considered the key factor frustrating efforts to halt the HIV epidemic. A proper understanding of HIV-1 genomic diversity is a fundamental prerequisite for proper epidemiology, genetic diagnosis, and successful drugs and vaccines design. Here, we report on the partial and near full-length genomic (NFLG) variability of HIV-1 isolates from a well-characterized cohort of recently infected patients in São Paul, Brazil.MethodologyHIV-1 proviral DNA was extracted from the peripheral blood mononuclear cells of 113 participants. The NFLG and partial fragments were determined by overlapping nested PCR and direct sequencing. The data were phylogenetically analyzed.ResultsOf the 113 samples (90.3% male; median age 31 years; 79.6% homosexual men) studied, 77 (68.1%) NFLGs and 32 (29.3%) partial fragments were successfully subtyped. Of the successfully subtyped sequences, 88 (80.7%) were subtype B sequences, 12 (11%) BF1 recombinants, 3 (2.8%) subtype C sequences, 2 (1.8%) BC recombinants and subclade F1 each, 1 (0.9%) CRF02 AG, and 1 (0.9%) CRF31 BC. Primary drug resistance mutations were observed in 14/101 (13.9%) of samples, with 5.9% being resistant to protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTI) and 4.9% resistant to non-NRTIs. Predictions of viral tropism were determined for 86 individuals. X4 or X4 dual or mixed-tropic viruses (X4/DM) were seen in 26 (30.2%) of subjects. The proportion of X4 viruses in homosexuals was detected in 19/69 (27.5%).ConclusionsOur results confirm the existence of various HIV-1 subtypes circulating in São Paulo, and indicate that subtype B account for the majority of infections. Antiretroviral (ARV) drug resistance is relatively common among recently infected patients. The proportion of X4 viruses in homosexuals was significantly higher than the proportion seen in other study populations.

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“…In Brazil, BF recombinants have increasing importance in the HIV epidemic [1], [2], [3], similar to South America [4], despite subtype C [5] prevalence in the country's south region. To date, 9 BF circulating recombinant forms (CRFs) are worldwide recognized, with 6 of them sampled in Brazil (CRF28_BF, CRF29_BF, CRF38_BF, CRF39_BF, CRF40_BF, and CRF46_BF; www.hiv.lanl.gov).…”

Section: Introductionmentioning

confidence: 99%

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

Iamarino¹,

Melo²,

Braconi³

et al. 2012

PLoS ONE

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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-naïve patients from the São 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-naïve 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.

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Short Communication:Molecular Characterization of HIV Type 1 BF Pol Recombinants from São Paulo, Brazil

Cited by 15 publications

References 25 publications

The role of recombination in the emergence of a complex and dynamic HIV epidemic

The role of recombination in the emergence of a complex and dynamic HIV epidemic

Characterization of Partial and Near Full-Length Genomes of HIV-1 Strains Sampled from Recently Infected Individuals in São Paulo, Brazil

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

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