Cellular immune selection with hepatitis C virus persistence in humans.
Cellular immune selection with hepatitis C virus persistence in humans.
复制标题
DOI：
10.1084/jem.20050121
复制
发表时间：
2005-06-06
期刊：
影响因子：
--
通讯作者：
Ray SC
中科院分区：
文献类型：
--
作者：
Cox AL;Mosbruger T;Mao Q;Liu Z;Wang XH;Yang HC;Sidney J;Sette A;Pardoll D;Thomas DL;Ray SC
丙型肝炎病毒（HCV）感染经常持续存在，尽管有大量的病毒特异性细胞免疫反应。为了确定免疫驱动的序列变异是否与HCV持续性有关，我们协调分析了序列进化和CD8+ T细胞对覆盖整个HCV多蛋白的表位的反应，这些受试者从感染前到一年后进行了前瞻性随访。在一名病毒血症清除的受试者感染后的一年内，没有出现T细胞表位的替换。相比之下，在持续性病毒血症和可检测到T细胞反应的受试者中，我们观察到69%的T细胞表位发生了替换，并且每个受试者至少有一个表位发生了替换。此外，氨基酸替换在T细胞表位内发生的频率是T细胞表位外的13倍（P < 0.001，范围5-38）。与初始序列相比，T淋巴细胞对10个突变肽中的8个的识别明显降低，表明病毒逃逸。在已知T细胞表位之外发生的16个非包膜替换中，8个代表转化为共识（P = 0.015）。这些发现揭示了HCV持续存在的两种不同的序列进化机制：病毒逃离CD8+ T细胞反应和复制能力的优化。
Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific cellular immune responses. To determine if immunologically driven sequence variation occurs with HCV persistence, we coordinately analyzed sequence evolution and CD8+ T cell responses to epitopes covering the entire HCV polyprotein in subjects who were followed prospectively from before infection to beyond the first year. There were no substitutions in T cell epitopes for a year after infection in a subject who cleared viremia. In contrast, in subjects with persistent viremia and detectable T cell responses, we observed substitutions in 69% of T cell epitopes, and every subject had a substitution in at least one epitope. In addition, amino acid substitutions occurred 13-fold more often within than outside T cell epitopes (P < 0.001, range 5–38). T lymphocyte recognition of 8 of 10 mutant peptides was markedly reduced compared with the initial sequence, indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These findings reveal two distinct mechanisms of sequence evolution involved in HCV persistence: viral escape from CD8+ T cell responses and optimization of replicative capacity.
登录
查看更多内容
影响因子：
32.4
作者：
Erickson, AL;Kimura, Y;Walker, CM
通讯作者：
Walker, CM
影响因子：
5.4
作者：
Allen, TM;Altfeld, M;Walker, BD
通讯作者：
Walker, BD
影响因子：
13.8
作者：
Jeanmougin, F;Thompson, JD;Gibson, TJ
通讯作者：
Gibson, TJ
影响因子：
56.9
作者：
Foy, E;Li, K;Gale, M
通讯作者：
Gale, M
影响因子：
11.8
作者：
Cox, AL;Netski, DM;Thomas, DL
通讯作者：
Thomas, DL