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Characteristics Of Genetic Variation Of Gag Gene Of HIV-1 Subtype B' In China

Posted on:2010-05-11Degree:MasterType:Thesis
Country:ChinaCandidate:X L ZhouFull Text:PDF
GTID:2144360278951775Subject:Immunology
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HIV-1 subtype B was the first identified subtype of the HIV-1 in the world and was prevailing in most countries in North America,Western Europe and south-east Asia,and its proportion of HIV-1 infected persons in those continents were 98.42%,87.62%and 38.00%, respectively.The HIV-1 B'strain derived from subtype B in United States was one of the main circulating HIV-1 strains in China.In this study,we collected 182 blood samples from former blood donors sampled from 2002 to 2008.The 182 full-length gag gene sequences were obtained after PCR amplified and sequenced.To investigate the difference between Chinese B'strains and US B strains and the mechanism of the variation occurred,the gag sequences were analyzed,together with 62 Chinese B' and 254 US B sequences downloaded from Los Alamos HIV sequence database.The phylogenetic analysis showed that all gag gene sequences obtained from patients belonged to B' strain and clustered in one branch.The Entropy score and average genetic distance of the sequences showed that the mutation rate of different segments in gag gene were changed smaller followed the order of p6,p2,p17,p1,p7,and p24.The entropy score of amino acid sites(n=258) in the CTL epitopes presented by HLA was significant higher than that of the amino acid sites(n=243) outside of the CTL epitopes(P=0.015).After analyzing the sequences in main homology region(MHR) and CypA binding loop,we found that 10.44%of samples had the R154K variation in MHR,and 18.68%or 15.38%of samples possessed the H87Q/P or V91l variation in CypA binding loop,respectively.The average entropy scores of Chinese B' sequences(n=244) and US B sequences (n=254) were 0.24 and 0.17,respectively,and the genetic variation of gag gene of US B was higher than that of Chinese B'.There existed significant difference in 111 amino acid sites between these two group sequences using the Entropy-Two tools.The increasing polymorphisms of the amino acids' composition were found in 25 sites,while the decreasing polymorphisms were found in other 86 sites.Of these sites,the amino acid residues at 17 sites changed in the consensus sequences.The amino acid at sites 76,79,94, 102,218 and 225 were found in previous studies,too.To investigate why the difference between Chinese B' and US B strain happened,we divided the Chinese B' sequences into three groups according to the samples collecting time. There existed 18 and 31 sites with significant difference in groupâ…¡(years 2004 and 2005) and groupâ…¢(years 2007 and 2008) sequences,compared to those in groupâ… (year 2002 and 2003).Of the 111 amino acid sites which found significant difference between US B and China B' sequences,the 13 amino acid sites were the same sites as those found in the analysis of the comparison in groups according to sampling time.The amino acid composition at sites 122,397 and 440 showed the increasing polymorphism,in which the amino acid at site 440 lies in the CTL epitope.The sites 122 and 397 were not yet published, and it needs further study to prove whether there existed new epitopes or not.The amino acid composition at sites 62,102,369 and 371 showed the decreasing polymorphism,all of them were located in the functional domain of gag gene.The sites 53,91,130,146,385 and 389 showed the opposite trend in amino acid compositions,which maybe imply the different selective pressures from the host or the surrounding environment.The genetic characteristic of the gag gene of the Chinese B' strains were analyzed systematically in this study,which laid the foundation for the research on the mechanism of HIV-1 CTL escape mutation,and provided the valuable data for the development of effective drugs and vaccines.
Keywords/Search Tags:HIV-1, subtype B, gag gene, genetic variation
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