To kill or to cure: options in host defense against viral infection.
It is generally thought that viral clearance is mediated primarily by antigen-specific T cell responses that destroy infected cells. This assumption may not be true for all viruses. Recent studies using a transgenic mouse model of hepatitis B virus infection have shown that adoptively transferred, virus-specific cytotoxic T cells can abolish hepatitis B virus gene expression and replication in the liver without killing the hepatocytes. This effect is mediated by interferon-gamma and tumor necrosis factor-alpha, which are secreted by the cytotoxic T lymphocytes following antigen recognition. Similar noncytopathic cytokine-dependent 'curative' processes also occur in this model during an unrelated infection of the liver. Intracellular viral inactivation mechanisms such as these could greatly amplify the protective effects of the immune response. Research has also been carried out to clarify the relevance of curative versus destructive mechanisms of viral clearance in other models of viral infection.
Guidotti
L G
LG
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California92037, USA.
Chisari
F V
FV
D000818:Animals; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy; D014777:Virus Diseases / Q000276:immunology* / Q000628:therapy*; D017735:Virus Latency / Q000276:immunology*; D014780:Viruses / Q000276:immunology* / Q000472:pathogenicity