Open AccessViral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver.
Author(s) -
Luca G. Guidotti,
Persephone Borrow,
Monte V. Hobbs,
Brent Matzke,
Ion Gresser,
Michael B. A. Oldstone,
Francis V. Chisari
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.10.4589
Subject(s) - lymphocytic choriomeningitis , ctl* , virology , hepatitis b virus , virus , viral replication , biology , permissiveness , immunology , cytotoxic t cell , hepatitis b virus pre beta , antigen , cd8 , hepatitis b virus dna polymerase , biochemistry , in vitro
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.