VIRAL CROSS-TALK - INTRACELLULAR INACTIVATION OF THE HEPATITIS-B VIRUS DURING AN UNRELATED VIRAL-INFECTION OF THE LIVER

Hepatitis B virus (HBV) infection is thought to be controlled by virus -specific cytotoxic T lymphocytes (CTL). We have recently shown that H BV-specific CTL can abolish HBV replication noncytopathically in the l iver 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) inf ection, and we show that this process is mediated by TNF-alpha and IFN -alpha/beta produced by LCMV-infected hepatic macrophages. These resul ts 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 superinf ected 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 conceptuall y similar events may be operative in other viral infections as well.