Guidotti L G, Borrow P, Hobbs M V, Matzke B, Gresser I, Oldstone M B, Chisari F V
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1996 May 14;93(10):4589-94. doi: 10.1073/pnas.93.10.4589.
Hepatitis B virus (HBV) infection is thought to be controlled by virus-specific cytotoxic T lymphocytes (CTL). We have recently shown that HBV-specific CTL can abolish HBV replication noncytopathically in the liver of transgenic mice by secreting tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) after antigen recognition. We now demonstrate that hepatocellular HBV replication is also abolished noncytopathically during lymphocytic choriomeningitis virus (LCMV) infection, and we show that this process is mediated by TNF-alpha and IFN-alpha/beta produced by LCMV-infected hepatic macrophages. These results confirm the ability of these inflammatory cytokines to abolish HBV replication; they elucidate the mechanism likely to be responsible for clearance of HBV in chronically infected patients who become superinfected by other hepatotropic viruses; they suggest that pharmacological activation of intrahepatic macrophages may have therapeutic value in chronic HBV infection; and they raise the possibility that conceptually similar events may be operative in other viral infections as well.
乙型肝炎病毒（HBV）感染被认为受病毒特异性细胞毒性T淋巴细胞（CTL）控制。我们最近发现，HBV特异性CTL在识别抗原后通过分泌肿瘤坏死因子α（TNF-α）和干扰素γ（IFN-γ），可在转基因小鼠肝脏中以非细胞病变方式消除HBV复制。我们现在证明，在淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染期间，肝细胞中的HBV复制也以非细胞病变方式被消除，并且我们表明这一过程由LCMV感染的肝巨噬细胞产生的TNF-α和IFN-α/β介导。这些结果证实了这些炎性细胞因子消除HBV复制的能力；阐明了在慢性感染患者被其他嗜肝病毒重叠感染时可能负责清除HBV的机制；提示肝内巨噬细胞的药理激活在慢性HBV感染中可能具有治疗价值；并提出在其他病毒感染中可能也存在概念上类似事件的可能性。
