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

ABSTRACT: Inter-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.The 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.Taken 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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC2855530 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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

Zhang Ming M Foley Brian B Schultz Anne-Kathrin AK Macke Jennifer P JP Bulla Ingo I Stanke Mario M Morgenstern Burkhard B Korber Bette B Leitner Thomas T

Retrovirology 20100323

<h4>Background</h4>Inter-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.<h4>Results</h4>The circulating recombinant form CRF02_AG, common in West Central Africa, appears to resul ...[more]

PMID: 20331894

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Project description:BackgroundEpidemic HIV-2 (groups A and B) emerged in humans circa 1930-40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985-91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread. Male circumcision (MC) is known to correlate negatively with HIV-1 prevalence in Africa, but studies examining this issue for HIV-2 are lacking.MethodsWe reviewed published HIV-2 serosurveys for 30 cities of all West African countries and obtained credible estimates of real prevalence through Bayesian estimation. We estimated past MC rates of 218 West African ethnic groups, based on ethnographic literature and fieldwork. We collected demographic tables specifying the ethnic partition in cities. Uncertainty was incorporated by defining plausible ranges of parameters (e.g. timing of introduction, proportion circumcised). We generated 1,000 sets of past MC rates per city using Latin Hypercube Sampling with different parameter combinations, and explored the correlation between HIV-2 prevalence and estimated MC rate (both logit-transformed) in the 1,000 replicates.Results and conclusionsOur survey reveals that, in the early 20th century, MC was far less common and geographically more variable than nowadays. HIV-2 prevalence in 1985-91 and MC rates in 1950 were negatively correlated (Spearman rho = -0.546, IQR: -0.553--0.546, p≤0.0021). Guinea-Bissau and Côte d'Ivoire cities had markedly lower MC rates. In addition, MC was uncommon in rural southwestern Côte d'Ivoire in 1930.The differential HIV-2 spread in West Africa correlates with different historical MC rates. We suggest HIV-2 only formed early substantial foci in cities with substantial uncircumcised populations. Lack of MC in rural areas exposed to bushmeat may have had a role in successful HIV-2 emergence.

Project description:In sub-Saharan Africa, endemic Kaposi’s sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi’s sarcoma (EpKS) resulting from the on-going HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ART-treated and -naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs. –naïve EpKS and male vs. female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r=0.83, p<10-10). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with the absence of HIV-1 transcripts in EpKS may suggest an indirect or systemic effect of HIV-1 to promote KS tumorigenesis.

Dataset Information

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

Publications

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

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