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Multilayered defense in HLA-B51-associated HIV viral control.

Zhang, YongHong; Peng, YanChun; Yan, HuiPing; Xu, Keyi; Saito, Masumichi; Wu, Hao; Chen, XinYue; Ranasinghe, Srinika; Kuse, Nozomi; Powell, Tim; Zhao, Yan; Li, WeiHua; Zhang, Xin; Feng, Xia; Li, Ning; Leligdowicz, Aleksandra; Xu, XiaoNing; John, Mina; Takiguchi, Masafumi; McMichael, Andrew; Rowland-Jones, Sarah; Dong, Tao.
J Immunol; 187(2): 684-91, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21670313
Polymorphism in the HLA region of a chromosome is the major source of host genetic variability in HIV-1 outcome, but there is limited understanding of the mechanisms underlying the beneficial effect of protective class I alleles such as HLA-B57, -B27, and -B51. Taking advantage of a unique cohort infected with clade B' HIV-1 through contaminated blood, in which many variables such as the length of infection, the infecting viral strain, and host genetic background are controlled, we performed a comprehensive study to understand HLA-B51-associated HIV-1 control. We focused on the T cell responses against three dominant HLA-B51-restricted epitopes: Gag327-345(NI9) NANPDCKTI, Pol743-751(LI9) LPPVVAKEI, and Pol283-289(TI8) TAFTIPSI. Mutations in all three dominant epitopes were significantly associated with HLA-B51 in the cohort. A clear hierarchy in selection of epitope mutations was observed through epitope sequencing. L743I in position 1 of epitope LI9 was seen in most B51(+) individuals, followed by V289X in position 8 of the TI8, and then, A328S, in position 2 of the NI9 epitope, was also seen in some B51(+) individuals. Good control of viral load and higher CD4(+) counts were significantly associated with at least one detectable T cell response to unmutated epitopes, whereas lower CD4(+) counts and higher viral loads were observed in patients who had developed escape mutations in all three epitopes or who lacked T cell responses specific to these epitope(s). We propose that patients with HLA-B51 benefit from having multiple layers of effective defense against the development of immune escape mutations.
Selo DaSilva