Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein.
Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein.
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DOI：
10.1084/jem.20011124
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发表时间：
2002-01-07
影响因子：
15.3
通讯作者：
Valiante, Nicholas M
中科院分区：
文献类型：
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作者：
Crotta, Stefania;Stilla, Annalisa;Wack, Andreas;D'Andrea, Annalisa;Nuti, Sandra;D'Oro, Ugo;Mosca, Marta;Filliponi, Franco;Brunetto, R Maurizia;Bonino, Ferruccio;Abrignani, Sergio;Valiante, Nicholas M
针对丙型肝炎病毒（HCV）的免疫响应很少有效地清除病毒，在这里报告了约17亿个慢性HCV感染CD81由HCV的主要包膜蛋白（HCV-E2）或抗CD81抗体阻止NK细胞活化，细胞因子的产生，细胞毒性颗粒释放和增殖使用激活的NK细胞观察到抑制作用，包括NK样T细胞克隆，包括表达NK细胞的受体，CD81连接CD81在NK细胞上的共同信号。与与NK细胞抑制受体相关的负面信号传导途径不同。结果暗示HCV-E2介导的NK细胞抑制是针对NK细胞早期抗病毒活性的有效HCV进化策略，并允许病毒作为慢性感染。
The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in ∼170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection.