Viral cross talk: Intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver
Viral cross talk: Intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver
复制标题
DOI：
10.1073/pnas.93.10.4589
复制
发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Chisari, FV
中科院分区：
文献类型：
--
作者：
Guidotti, LG;Borrow, P;Chisari, FV
乙型肝炎病毒（HBV）感染被认为是由病毒特异性细胞毒性T淋巴细胞（CTL）控制的。我们最近发现，HBV特异性CTL可以在抗原识别后通过分泌肿瘤坏死因子α (tnf - α)和干扰素γ (ifn - γ)，在转基因小鼠的肝脏中非细胞病变地消除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HBV复制也被非细胞病变性地消除，并且我们表明这一过程是由LCMV感染的肝巨噬细胞产生的tnf - α和ifn - α / β介导的。这些结果证实了这些炎性细胞因子消除HBV复制的能力；它们阐明了被其他嗜肝病毒重复感染的慢性感染患者清除HBV的可能机制；提示肝内巨噬细胞的药理激活可能对慢性HBV感染具有治疗价值；他们提出了一种可能性，即概念上类似的事件也可能在其他病毒感染中发生。
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.