Guidotti L G, Ishikawa T, Hobbs M V, Matzke B, Schreiber R, Chisari F V
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Immunity. 1996 Jan;4(1):25-36. doi: 10.1016/s1074-7613(00)80295-2.
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.
人们普遍认为，病毒清除主要是由细胞毒性T淋巴细胞（CTL）对感染细胞的破坏介导的。在本报告中，我们使用乙型肝炎病毒（HBV）复制的转基因小鼠模型来证明这一假设可能并非适用于所有病毒。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的HBV基因表达和复制。这种抗病毒功能是由CTL分泌的干扰素γ（IFNγ）和肿瘤坏死因子α（TNFα）介导的，或者是由它们在抗原识别后激活的抗原非特异性巨噬细胞和T细胞介导的。这些细胞因子激活两条独立的杀病毒途径：第一条途径消除HBV核衣壳颗粒及其携带复制病毒基因组的内容物，而第二条途径使病毒RNA不稳定。像这样的细胞内病毒失活机制可以极大地放大免疫反应的保护作用，而这种机制的失败可能导致病毒持续存在或宿主死亡。
