Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Selected amino acid mutations in HIV-1 B subtype gp41 are Associated with Specific gp120V3 signatures in the regulation of CoReceptor usage. | Dimonte et al. Retrovirology 2011 8 33 http content 8 1 33 RETROVIROLOGY RESEARCH Open Access Selected amino acid mutations in HIV-1 B subtype gp41 are Associated with Specific gp120V3 signatures in the regulation of CoReceptor usage Salvatore Dimonte1 Fabio Mercurio1 Valentina Svicher1 Roberta D Arrigo2 Carlo-Federico Perno1 2 and Francesca Ceccherini-Silberstein1 Abstract Background The third variable loop V3 of the HIV-1 gp120 surface protein is a major determinant of cellular coreceptor binding. However HIV-1 can also modulate its tropism through other regions in gp120 such as V1 V2 and C4 regions as well as in the gp41 protein. Moreover specific changes in gp41 are likely to be responsible for of damage in gp120-CCR5 interactions resulting in potential resistance to CCR5 inhibitors. In order to genetically characterize the two envelope viral proteins in terms of co-receptor usage we have analyzed 526 full-length env sequences derived from HIV-1 subtype-B infected individuals from our and public Los Alamos databases. The co-receptor usage was predicted by the analysis of V3 sequences using Geno2Pheno G2P algorithm. The binomial correlation phi coefficient was used to assess covariation among gp120V3 and gp41 mutations subsequently the average linkage hierarchical agglomerative clustering was performed. Results According to G2P false positive rate FPR values among 526 env-sequences analyzed we further characterized 196 sequences 105 with FPR 5 and 91 with FPR 70 for X4-using and R5-using viruses respectively. Beyond the classical signatures at 11 25 V3 positions S11S and E25D R5-tropic viruses S11KR and E25KRQ X4-tropic viruses other specific V3 and gp41 mutations were found statistically associated with the co-receptor usage. Almost all of these specific gp41 positions are exposed on the surface of the glycoprotein. By the covariation analysis we found several statistically significant associations between V3 and gp41 mutations especially
