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Adaptive Evolution Of HIV-1 And A/H1N1 And Evaluation Of Bootscan Analysis Of HIV-1 Recombination

Posted on:2011-09-14Degree:MasterType:Thesis
Country:ChinaCandidate:N DingFull Text:PDF
GTID:2144360302993736Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Genetic evolution and recombination play a very important role in the transmission,infection and pathogenesis of virus.In this study, adaptive evolution of HIV-1 with different coreceptor tropisms and subtypes,and molecular evolution of Influenza A H1N1(A/H1N1) were performed by classical evolutionary biology methods.In addition,we evaluated the bootscanning method for HIV-1 recombination analysis, and reanalyzed the recombination map of CRF03_AB.The major results are as follows:1.We performed a genome-wide comparison between the adaptive evolutions of different coreceptor tropism variants across HIV-1 subtypes B and C.The results show that both R5 and X4 variants experience differential evolutionary patterns and differential HIV-1 genes suffer differential positive selection pressures,suggesting complex selection pressures driving HIV-1 evolution.Compared to other hypervariable regions of Gpl20,significantly more positively selected sites were detected in V3 region of subtype B X4 variants,V2 region of subtype B R5 variants,and V1 and V4 regions of subtype C X4 variants,distinctly indicating an association of positive selection with coreceptor recognition/binding.Intriguingly,significantly higher proportion (33.3%-55.6%,P<0.05) of positively selected sites are identified in the C3 region than other conserved regions of Gp120 in all analyzed HIV-1 variants,indicating that C3 region may be more important to HIV-1 adaptation than recognized previously.In addition,approximately half of positively selected sites identified in Env genes are identical between R5 and X4 variants.These mutual positively selected sites might not only suggest a functional importance in viral survival and adaptation,but also imply a potential cross-immunogenicity between both HIV-1 R5 and X4 variants,which has important implications for AIDS vaccine development.2.We confirmed that the influenza A H1N1(A/H1N1) viruses originated from the reassortment of previous triple-reassortant swine influenza viruses including genomic segments from both avian and human lineages with North American and Eurasian swine lineages.The longer phylogenetic branch length to their nearest genetic neighbors indicates that the origin of influenza A/H1N1 is unlikely to be a very recent event.In addition,influenza A/H1N1 suffered strong purifying selection among human population.Seventy six new unique mutations are found to be exclusively fixed in the influenza A H1N1 virus lineages, suggesting a potential role of selective sweep in the early evolution of this virus.3.We re-analyzed 11 previously characterized HIV-1 CRFs using SimPlot software to evaluate bootscan analysis of HIV-1 recombination. We found that the crossovers determined under 250,300 and 350 nt windows,especially under 300 nt window and moving a step with 10nt are significantly closer to hypothetical breakpoint(P<0.01).These suggest that these parameters are the preferential selection for HIV-1 recombination analysis.HIV-1 strains prevailing in the same geographic areas with HIV-1 inter-subtype recombinants are believed to have chance to participate in recombination events.When HIV-1 reference strains from recombinant-prevailing areas were applied,identified recombination patterns were well supported by phylogenetic analyses.Therefore,in bootscan analysis HIV-1 subtype references should be selected from recombinant-prevailing areas.We reanalyzed HIV-1 CRF03_AB using Simplot under the preferential parameter mentioned above,and found that a small previously unknown mosaic segment belonged to subtype A.
Keywords/Search Tags:HIV-1, Influenza A (H1N1), coreceptor tropism, adaptive evolution, positive selection, circulating recombinant forms (CRFs)
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