Intracellular hepatitis B virus nucleocapsids survive cytotoxic T-lymphocyte-induced apoptosis.
Following antigen recognition, hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL) induce a necroinflammatory liver disease in HBV-transgenic mice. An early event in this process is CTL-dependent activation of apoptosis in a small fraction of HBV-positive hepatocytes. Here we show that cytoplasmic HBV nucleocapsids and their cargo of replicative DNA intermediates survive CTL-induced apoptosis of hepatocytes in vitro. These results suggest that destruction of infected cells per se is not sufficient to destroy the replicating HBV genome in infected tissue and that other events in addition to this process are required for viral clearance to occur.
Pasquetto
V
V
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Wieland
S
S
Chisari
F V
FV
D000818:Animals; D017209:Apoptosis; D004279:DNA, Viral / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D008099:Liver / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D019251:Nucleocapsid / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens