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

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  • 1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
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    • Guidotti LG 1
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Proceedings of the National Academy of Sciences of the United States of America, 01 May 1996, 93(10):4589-4594
https://doi.org/10.1073/pnas.93.10.4589 PMID: 8643448 PMCID: PMC39321

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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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Proc Natl Acad Sci U S A. 1996 May 14; 93(10): 4589–4594.
PMCID: PMC39321
PMID: 8643448

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

L G Guidotti, P Borrow, M V Hobbs, B Matzke, I Gresser, M B Oldstone, and F V Chisari
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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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Selected References

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