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Journal of Virology, May 2000, p. 4483-4494, Vol. 74, No. 10
Molecular Virology and Hepatology Research,
Division of Basic Medical Sciences,1 and
Division of Pathology,2 Faculty of
Medicine, Health Sciences Centre, Memorial University of
Newfoundland, St. John's, Newfoundland A1B 3V6, Canada
Received 15 November 1999/Accepted 17 February 2000
Woodchuck hepatitis virus (WHV), similar to human hepatitis B
virus, causes acute liver inflammation that can progress to chronic
hepatitis and hepatocellular carcinoma. WHV also invades cells of the
host lymphatic system, where it persists for life. We report here that
acute and chronic hepadnavirus hepatitis is characterized by a profound
difference in the expression of class I major histocompatibility
complex (MHC) molecules on the surface of infected hepatocytes and,
notably, lymphoid cells. While acute WHV infection is accompanied by
the enhanced hepatocyte surface presentation of class I MHC antigen and
upregulated transcription of the relevant hepatic genes, inhibition of
class I antigen display on liver cells is a uniform hallmark of chronic
WHV infection. This inhibition in chronic hepatitis occurs despite
augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain,
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Copyright © 2000, American Society for Microbiology. All rights reserved.
Posttranscriptional Inhibition of Class I Major
Histocompatibility Complex Presentation on Hepatocytes and Lymphoid
Cells in Chronic Woodchuck Hepatitis Virus Infection
2-microglobulin, and transporters
associated with antigen processing (TAP1 and TAP2). Further, the class
I antigen inhibition is not related to the histological severity of
hepatocellular injury, the extent of lymphocytic infiltrations, the
level of intrahepatic gamma interferon induction, or the hepatic WHV
load. Importantly, the antigen expression is also inhibited on organ
lymphoid cells of chronically infected hosts. The results obtained in
this study demonstrate that the defective presentation of class I MHC
molecules on cells supporting persistent WHV replication is due to
viral posttranscriptional interference. This event may diminish the
susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the
class I MHC-dependent functions of the host immune system. This
multifarious effect could be critical for perpetuation of liver damage
and evasion of the antiviral immunological surveillance in chronic
infection and therefore could be supportive of hepadnavirus persistence.
*
Corresponding author. Mailing address: Molecular
Virology and Hepatology Research, Division of Basic Medical Sciences,
Faculty of Medicine, Health Sciences Centre, Memorial University of
Newfoundland, St. John's, NFLD, Canada A1B 3V6. Phone: (709) 737-7301 (office) or (709) 737-7214 (lab). Fax: (709) 737-2228. E-mail:
timich{at}morgan.ucs.mun.ca.
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