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 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.
Guidotti
L G
LG
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Borrow
P
P
Hobbs
M V
MV
Matzke
B
B
Gresser
I
I
Oldstone
M B
MB
Chisari
F V
FV
D000818:Animals; D005260:Female; D015870:Gene Expression; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta