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Distribution Of The Integrin α4β7Binding Sites In HIV Infections

Posted on:2013-03-24Degree:MasterType:Thesis
Country:ChinaCandidate:B ZhangFull Text:PDF
GTID:2254330422464132Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
Objective: HIV-1infection mechanism and spread of the virus is frontier and hotof HIV research. HIV-1envelope protein binds to and signals through integrin α4β7,the gut mucosal homing receptor for peripheral T cells. This binding has greatinfluence in infection, replication and dissemination of virus. At present, in China,Sexual transmission and IDU (Intraveneous Drug Users)is the main mode oftransmission in HIV infection. Sexually transmitted in the first place and there isgrowing trend. This study will identify the polymorphism of integrin α4β7bindingsite in HIV-1individuals infected through sexual contacts, and determine whetherthere exists selectivity or not in this population.Methods: The experimental samples choose the Positive plasma samples withheterosexual transmission and IDU of the Sichuan Liangshan the subtype ofCRF07_BC. Nested PCR amplification gp120V1-V5, entropy value and the ratio ofnon-synonymous and synonymous (dN/dS) compare sequence differences of the twogroups. Phylogenetic Tree is reconstructed by Neighbor-joining method, maximumlikelihood method and the Bayesian method, to view the Sequence classification andevolution.Results: The results are206sequences. Heterosexual transmission has103sequences; IDU has103sequences. In the two groups integrin α4β7binding sites of191sequences are LDI, accounted for92.7%of the total sequence. The tripeptidedistribution in the population of IDU:93sequences are LDI,5sequences are LDV,and2sequences are LDM,1sequence is VDV,1sequence is LDL, the Shannon’sdiversity index is0.45. The tripeptide distribution in the population of heterosexual:98sequences are LDI,1sequence is LDV, and1sequence is LDM,1sequence is TDI,1sequence is VDI, the Shannon’s diversity index is0.27. The Shannon index of theIDU is greater than the heterosexual, so the α4β7binding sites of IDU have higherdiversity. By calculating the entropy, in the population level,6sites entropy value ofIDU is higher than the heterosexual,11sites entropy value of the heterosexual is higher than IDU. The entropy value of heterosexual is higher than IDU; the aminoacid variation of heterosexual is bigger. In integrin α4β7binding sites of the threeamino acids (29,30,31) the entropy value at the amino acid31is high, the Twogroups has significant difference in this site, so the heterosexual population hasselectivity in this site. under selection pressure IDU have7positive selection sites ofsignificant difference and25negative selection sites; heterosexual population have9positive selection sites and58negative selection sites. On the population levelheterosexual have more selection sites. In the integrin α4β7binding sites ofheterosexual each amino acid dN/dS is lower than IDU. Taking IDU for control,heterosexual exist selectivity at the30th and31th site (P<0.05). By constructingphylogenetic tree in three ways, we can determine the analytical data are CRF07_BCsubtypes and these patients have no correlation dissemination.Conclusion: Based on the experimental study the following conclusions can bedrawn: The integrin α4β7binding site in CRF07_BC mainly distribution is LDI; Inthe population level, heterosexual have more sites to choose; Integrin α4β7bindingsite exists selectivity in heterosexual population; In this study, the isolates of the mostrecent common ancestor is India C, the recent ancestors strain origin time is1976.
Keywords/Search Tags:Human immunodeficiency virus type1, Integrin α4β7, Heterosexual, IDU, Phylogenetic tree
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