Document 0668
 DOCN  M9650668
 TI    Intracellular inactivation of the hepatitis B virus by cytotoxic T
       lymphocytes.
 DT    9605
 AU    Guidotti LG; Ishikawa T; Hobbs MV; Matzke B; Schreiber R; Chisari FV;
       Department of Molecular and Experimental Medicine, Scripps; Research
       Institute, La Jolla, California 92037, USA.
 SO    Immunity. 1996 Jan;4(1):25-36. Unique Identifier : AIDSLINE
       GENBANK/J03590
 AB    It is widely believed that viral clearance is mediated principally by
       the destruction of infected cells by CTLs. In this report, we use a
       transgenic mouse model of HBV replication to demonstrate that this
       assumption may not be true for all viruses. We find that adoptively
       transferred virus-specific CTLs can abolish HBV gene expression and
       replication in the liver without killing the hepatocytes. This antiviral
       function is mediated by IFN gamma and TNF alpha secreted by the CTL or
       by the antigen-nonspecific macrophages and T cells that they activate
       following antigen recognition. These cytokines activate two independent
       virocidal pathways: the first pathway eliminates HBV nucleocapsid
       particles and their cargo of replicating viral genomes, while the second
       pathway destabilizes the viral RNA. Intracellular viral inactivation
       mechanisms such as these could greatly amplify the protective effects of
       the immune response, while failure of such mechanisms could lead to
       viral persistence or to the death of the host.
 DE    Animal  CD8-Positive T-Lymphocytes/*IMMUNOLOGY/TRANSPLANTATION/VIROLOGY
       Gene Expression Regulation, Viral  Hepatitis B/*IMMUNOLOGY/THERAPY
       Hepatitis B Surface Antigens/ANALYSIS  Hepatitis B Virus/*PHYSIOLOGY
       *Immunotherapy, Adoptive  Interferon Type II/SECRETION
       Liver/*IMMUNOLOGY/PATHOLOGY/VIROLOGY  Mice  Mice, Transgenic  Molecular
       Sequence Data  Support, U.S. Gov't, P.H.S.  Tumor Necrosis
       Factor/SECRETION  Virus Replication/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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