| Former plasma donors (FPDs) who live in Henan and contiguous provinces ofcentral China and injecting drug users (IDUs) in provinces in southwest and northwestChina represent the major hig-risk populations for HIV prevalence all over the country.China is facing the crisis that HIV is spreading from high risk population to commonpopulation by several transmission pathways. To characterize current HIV-1prevalence, we collected 508 HIV-1 sero-positive blood samples from Henan, Shanxi, Sichuan and Xinjiang provinces between August 2003 to September 2005 andsequences were successfully obtained by nested-PCR and subsequent auto-sequencing.GCG software package and online sequence analysis tools were used to editsequences and analyze genotype, genetic distance, amino acid sequences, antigenepitopes, N-linked glycosylation sites and coreceptor. In this paper, we analyzed thefull-length gp120, gag, nef and tat. We observed: 1) Genetic diversity. Thailand B isthe major strain circulating in FPDs in Henan and Shanxi provinces whereasCRF07_BC strain is predominantly circulating in IDUs in Sichuan and Xinjiangprovinces. The analysis of genetic distances revealed that C3 regions of B' clade andCRFO7_BC are more variable than other conservative regions; there is significantdifference in V1 and V4 regions between B' strains from Henan and from Shanxiprovinces; the genetic distance culminates in P17 region in B' strains derived Gagwhereas P1P6 represents the most variable region in CRF07_BC gag gene. 2)Characteristics in amino acid sequences. Regional specific amino acid motifs wereidentified in gp120, gag and tat of B' strains and gp120, gag, nef and tat ofCRF07_BC strains. 3) Variation at the tip, N-linked glycosites of V3 loop andcoreceptor binding sites. 6 different motifs were defined at the tip of B' derived V3loop, among those GPGQ accounts for 43.59ï¼…cases, whereas 4 motifs co-exist at thetip of CRF07_BC V3 loop and 96.06ï¼…cases contain GPGQ sequences. The losingrate of N-linked glycosites is higher at V3 loop in B' subtype strains than CRF07_BC. 14.1ï¼…B' strains and 86.7ï¼…CRF07_BC strains contain CCR5 motif. 4) Antigenepitopes. The sequences at CTL epitopes are more consistent in B' strains than that atneutralization epitopes. 5) Deletion in P6. A deletion of 1-13 amino acids wasfrequently observed at the central region of p6 in CRF07_BC derived Gag, and nosignificant differences in CD4~+ counts and virus loads were observed betweensubjects infected by viral strains with/without this deletion.From those results above, we concluded: 1) Different HIV-1 clades areconsistently circulating in different big-risk populations and thereby resulted insegregated HIV-1 strain specific prevalence. C3 is the most variable region amongconservative regions of B' and CRF07_BC strains. 2) The regional HIV-1 prevalencemay be initiated by regional specific ancestor viral strain, inter-province exchange ofviral strains was rare. 3) B' clade may undertake more immune pressure thanCRF07_BC, which resulted in more variations at the tip and N-linked glycosites ofV3 loop. 4) The antigen epitopes of B' genotype strains in China are more identical toknown CTL epitopes than to neutralization epitope, 5) The deletion of 1-13 aminoacids in gag P6 region of CRF07_BC strains has little influence to viral replicationand fitness.
|
PDF Full Text Request