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. 1996 May 14;93(10):4589–4594. doi: 10.1073/pnas.93.10.4589

Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver.

L G Guidotti 1, P Borrow 1, M V Hobbs 1, B Matzke 1, I Gresser 1, M B Oldstone 1, F V Chisari 1
PMCID: PMC39321  PMID: 8643448

Abstract

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.

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