Analysis of Near Full-Length Genome Sequences of HIV Type 1 BF Intersubtype Recombinant Viruses from Brazil Reveals Their Independent Origins and Their Lack of Relationship to CRF12_BF

Area de Patogenia Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III. Ctra. Majadahonda-Pozuelo, Km. 2. 28220 Majadahonda (Madrid), Spain.
AIDS Research and Human Retroviruses (Impact Factor: 2.33). 11/2004; 20(10):1126-33. DOI: 10.1089/aid.2004.20.1126
Source: PubMed


We analyze the recombinant structures and phylogenetic relationships of nine near full-length genome sequences of HIV-1 BF intersubtype recombinant viruses from Brazil, eight of them newly derived. These were obtained by PCR amplification from peripheral blood mononuclear cells (PBMCs) DNA or PBMCs culture supernantant RNA. The recombinants exhibited unique mosaic structures, except two viruses with a single near coincident breakpoint. Comparison with CRF12_BF revealed only two coincident breakpoints in two recombinants. Phylogenetic analyses failed to support a common ancestry of Brazilian recombinants or their relationship to CRF12_BF, which widely circulates in Argentina. Intersubtype breakpoint distribution along the genome was uneven, with the highest mean frequency in the polymerase domain of reverse transcriptase, and the lowest in env. These results indicate that HIV-1 BF recombinants from Brazil have independent origins and are unrelated to CRF12_BF, and that intersubtype breakpoints are frequent in pol segments analyzed for drug resistance detection.

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    • "Once more, our findings are in agreement with the distribution of HIV-1 subtypes in the Brazilian epidemic. The Southeast is a region where subtypes B and F co-circulate, in this manner recombinants between these two subtypes can be expected [53], [66]. "
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    ABSTRACT: The present study investigated the prevalence of HIV-1 multiple infections in a population composed by 47 patients under HAART failure and enrolled at the National DST/AIDS, Program, Ministry of Health, Brazil.Detection of multiple infections was done using a previously published RFLP assay for the HIV-1 protease gene, which is able of distinguishing between infections caused by a single or multiple HIV-1 subtypes. Samples with multiple infections were cloned, and sequence data submitted to phylogenetic analysis. We were able to identify 17 HIV-1 multiple infections out of 47 samples. Multiple infections were mostly composed by a mixture of recombinant viruses (94%), with only one case in which protease gene pure subtypes B and F were recovered. This is the first study that reports the prevalence of multiple infections and intersubtype recombinants in a population undergoing HAART in Brazil. Based on the data there was a steep increase of multiple infections after the introduction of the combined antiretroviral therapy in Brazil. Cases of multiple infections may be associated with HIV-1 genetic diversity through recombination allowing for the generation of viruses showing a combination of resistance mutations.
    Full-text · Article · Jan 2014 · PLoS ONE
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    • "New and novel URFs are highly prevalent, and are markedly evident in Africa,43,48,49 South America,50 Cuba,51 China52,53 and Southeast Asia.25,24,27 They can continue to spread in the population, and lead to the emergence of new CRFs. "
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    ABSTRACT: One of the major characteristics of HIV-1 is its high genetic variability and extensive heterogeneity. This characteristic is due to its molecular traits, which in turn allows it to vary, recombine, and diversify at a high frequency. As such, it generates complex molecular forms, termed recombinants, which evade the human immune system and so survive. There is no sequence constraint to the recombination pattern as it appears to occur at inter-group (between groups M and O), as well as interand intra-subtype within group M. Rapid emergence and active global transmission of HIV-1 recombinants, known as circulating recombinant forms (CRFs) and unique recombinant forms (URFs), requires urgent attention. To date, 55 CRFs have been reported around the world. The first CRF01_AE originated from Central Africa but spread widely in Asia. The most recent CRF; CRF55_01B is a recombinant form of CRF01_AE and subtype B, although its origin is yet to be publicly disclosed. HIV-1 recombination is an ongoing event and plays an indispensable role in HIV epidemics in different regions. Africa, Asia and South America are identified as recombination hot-spots. They are affected by continual emergence and cocirculation of newly emerging CRFs and URFs, which are now responsible for almost 20% of HIV-1 infections worldwide. Better understanding of recombinants is necessary to determine their biological and molecular attributes.
    Full-text · Article · Jun 2013 · Infectious disease reports
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    • "Phylogenetic analysis of previously characterised B/F recombinant HIV-1 sequences showed that all of the sequences of the 13 subjects grouped in the same cluster as B/F recombinant sequences of various South American origins, and showed a close relationship with South American CRF12_BF [Foglieni et al., 2010]. Two recently described BF URFs from Luxemburg and Brazil (accession numbers EU170145 and AY455780 [Thomson et al., 2004]) were the closest to this strain. All of the sequences have been deposited in GenBank under accession numbers HQ834729-HQ834742. "
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    ABSTRACT: Migratory processes have caused changes in human immunodeficiency virus (HIV) epidemiology and non-B subtypes are now playing an increasing role. In a cohort of 553 HIV-infected outpatients tested to identify non-B isolates, the largest group consisted of 13 subjects with a recombinant B/F form (prevalence 2.4%). Sequencing and phylogenetic analyses described a B/F recombinant clade with anomalous breakpoints that did not allow it to be classified as CRF12_BF. Viral load was not quantified efficiently because of a mismatch in the primers and probes used by commercial assays. An assessment of the clinical management, and epidemiological, immunological, and virological characteristics of these patients, who were receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimens, showed that the immunological and virological mismatch delayed the start of treatment by a mean of 6.8 months. Therapy was started in nine patients. Both NNRTI- and PI-based regimens led to full virological suppression after a mean 36 weeks of treatment; the PI-based regimens proved to be more effective in terms of immunological recovery (1,341 vs. 544 CD4+ cells/mm(3) ). The spread of non-B subtypes is increasing throughout the world but their response to treatment is still unclear. PIs and NNRTIs are effective but further tests are needed to allow the more efficient recognition of these viral strains and establish how they should be treated.
    Preview · Article · Sep 2011 · Journal of Medical Virology
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