Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes
Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes
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DOI：
10.1016/s1074-7613(00)80295-2
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发表时间：
1996-01-01
期刊：
影响因子：
32.4
通讯作者：
Chisari, FV
中科院分区：
文献类型：
--
作者：
Guidotti, LG;Ishikawa, T;Chisari, FV
人们普遍认为，病毒清除主要是通过CTL破坏感染细胞来介导的。在这份报告中，我们使用转基因小鼠模型的HBV复制，以证明这一假设可能不是真的所有病毒。我们发现，过继转移的病毒特异性CTL可以在不杀死肝细胞的情况下消除肝脏中HBV基因的表达和复制。这种抗病毒功能由CTL分泌的IFN γ和TNF α或由抗原识别后激活的抗原非特异性巨噬细胞和T细胞介导。这些细胞因子激活两个独立的杀病毒途径：第一个途径消除HBV核衣壳颗粒及其复制病毒基因组的货物，而第二个途径使病毒RNA不稳定。细胞内的病毒灭活机制，如这些可以大大放大免疫反应的保护作用，而这种机制的失败可能会导致病毒的持久性或死亡的主机。
It is widely believed that viral clearance is mediated principally by the destruction of infected cells by CTLs. In this report, we use a transgenic mouse model of HBV replication to demonstrate that this assumption may not be true for all viruses. We find that adoptively transferred virus-specific CTLs can abolish HBV gene expression and replication in the liver without killing the hepatocytes. This antiviral function is mediated by IFN gamma and TNF alpha secreted by the CTL or by the antigen-nonspecific macrophages and T cells that they activate following antigen recognition. These cytokines activate two independent virocidal pathways: the first pathway eliminates HBV nucleocapsid particles and their cargo of replicating viral genomes, while the second pathway destabilizes the viral RNA. Intracellular viral inactivation mechanisms such as these could greatly amplify the protective effects of the immune response, while failure of such mechanisms could lead to viral persistence or to the death of the host.