Diversity of HIV-1 Subtype B Implications to the Origin of BF Recombinants 英文参考文献.docVIP

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Diversity of HIV-1 Subtype B Implications to the Origin of BF Recombinants 英文参考文献.doc

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Diversity of HIV-1 Subtype B Implications to the Origin of BF Recombinants 英文参考文献

DiversityofHIV-1SubtypeB:ImplicationstotheOrigin ofBFRecombinants Elcio′ Leal*,FabiolaE.Villanova FederalUniversityofPara′, Bele′m, Brazil Abstract Background:TheHIV-1subtypeBepidemicinBrazilispeculiarbecauseofthehighfrequencyofisolateshavingtheGWGR tetrameratV3loopregion.IthasbeensuggestedthatGWGRisadistinctvariantandlesspathogenicthanothersubtypeB isolates. Methodology/PrincipalFindings:Ninety-fourpercentoftheHIV-1subtypeBworldwidesequences(7689/8131)obtained fromtheLosAlamosHIVdatabasecontainprolineatthetetrameroftheV3loopoftheenvgene(GPGR)andonly0.74% (60/8131)havetryptophan(GWGR).Bycontrast,48.4%(161/333)ofsubtypeBisolatesfromBrazilhaveproline,30.6%(102/ 333) contain tryptophan and 10.5% (35/333) have phenylalanine (F) at the second position of the V3 loop tip. The proportionoftryptophanandphenylalanineinBrazilianisolatesismuchhigherthaninworldwidesubtypeBsequences (chi-squaretest,p=0.0001).Thecombinedproportionofproline,tryptophanandphenylalanine(GPGR+GWGR+GFGR)of Brazilian isolates corresponds to 89% of all amino acids in the V3 loop. Phylogenetic analysis revealed that almost all subtypeBisolatesinBrazilhaveacommonoriginregardlessoftheirmotif(GWGR,GPGR,GGGR,etc.)attheV3tetramer. This shared ancestral origin was also observed in CRF28_BF and CRF29_BF in a genome region (free of recombination) derived from parental subtype B. These results imply that tryptophan substitution (e.g., GWGR-to-GxGR), which was previouslyassociatedwiththechangeinthecoreceptorusagewithinthehost,alsooccursatthepopulationlevel. Conclusions/Significance:Basedonthecurrentfindingsandpreviousstudyshowingthattryptophanandphenylalaninein theV3looparerelatedwithcoreceptorusage,weproposethattryptophanandphenylalanineinsubtypeBisolatesinBrazil are kept by selective mechanisms due to the distinct coreceptor preferences in target cells of GWGR, GFGR and GFGR viruses. Citation: Leal E′, Villanova FE (2010) Diversity of HIV-1 Subtype B: Implications to the Origin of BF Recombinants. PLoS ONE