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Detection of Human Immunodeficiency Virus Type 1 (HIV-1) A/AE Circulating Recombinant Form (CRF) in India: Possible Implications.

ABSTRACT: BACKGROUND:Rapidly evolving viruses such as human immunodeficiency virus (HIV-1) develop marked sequence differences in their genome over the course of an epidemic and in individuals infected for longer duration. This is because of the error prone reverse transcriptase (RT), which rapidly incorporates mutations resulting in genomic diversity, altered cell tropism, immune escape, and variable resistance to antiretroviral drugs. As a result, radically different genomic combinations may be generated in individuals infected by genetically diverse viruses that have mosaic genomes. METHODS:Whole blood sample was collected from 25 HIV-1 infected patients. Chromosomal DNA was isolated from the patient's peripheral blood mononuclear cells (PBMCs). Full-length gag gene (~1.5 kb) was amplified. PCR products were subjected to direct automated sequencing. For identification of recombinants Simplot version 2.5 was used. RESULTS:Out of 25 gag genes that were sequenced, the gene amplified from a 29 years old HIV-1 seropositive male revealed a putative recombinant sequence. This sequence showed maximum homology with HIV-1 subtype A. Simplot analysis revealed the sequence to be a likely recombinant with the following composition: Initial stretch of 1 to 200 nucleotides representing AE circulating recombinant form (CRF), 201 to 440 nucleotides representing HIV-1 subtype A, 441 to 660 nucleotides representing AE CRF again, 661 to 700 nucleotides representing HIV-1 subtype A and the remaining stretch of the nucleotides from 701 to 1076 representing AE CRF. CONCLUSION:We document a putative HIV-1 subtype A/ AE CRF. It is important to monitor various CRFs that are being generated and horizontally spread in the community. This has significant implications for development of candidate vaccine for India.

SUBMITTER: Gupta RM

PROVIDER: S-EPMC5034182 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Detection of Human Immunodeficiency Virus Type 1 (HIV-1) A/AE Circulating Recombinant Form (CRF) in India: Possible Implications.

Gupta R M RM Seth P P Prasad Vvsp V Sahni A K AK Jena J J

Medical journal, Armed Forces India 20061001 4

<h4>Background</h4>Rapidly evolving viruses such as human immunodeficiency virus (HIV-1) develop marked sequence differences in their genome over the course of an epidemic and in individuals infected for longer duration. This is because of the error prone reverse transcriptase (RT), which rapidly incorporates mutations resulting in genomic diversity, altered cell tropism, immune escape, and variable resistance to antiretroviral drugs. As a result, radically different genomic combinations may be ...[more]

PMID: 27688530

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Project description:BackgroundAn increase in non-B HIV-1 infections among men who have sex with men (MSM) in the United Kingdom (UK) has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies.Methods and resultsA total of 55,556 pol (reverse transcriptase and protease) sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL). Overall 72 patients shared the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug users (IDUs). In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints), which has been classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST). This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a subtype B strain.ConclusionsWe report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around 1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B. These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously distinct MSM and heterosexual epidemics.

Project description:Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

Dataset Information

Detection of Human Immunodeficiency Virus Type 1 (HIV-1) A/AE Circulating Recombinant Form (CRF) in India: Possible Implications.

Publications

Detection of Human Immunodeficiency Virus Type 1 (HIV-1) A/AE Circulating Recombinant Form (CRF) in India: Possible Implications.

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