Posttranscriptional clearance of hepatitis B virus RNA by cytotoxic T lymphocyte-activated hepatocytes.
Using transgenic mice that replicate the hepatitis B virus (HBV) genome, we recently demonstrated that class I-restricted, hepatitis B surface antigen-specific cytotoxic T lymphocytes (CTLs) can noncytolytically eliminate HBV pregenomic and envelope RNA transcripts from the hepatocyte. We now demonstrate that the steady-state content of these viral transcripts is profoundly reduced in the nucleus and cytoplasm of CTL-activated hepatocytes, but their transcription rates are only slightly reduced. Additionally, we demonstrate that transcripts covering the HBV X coding region are resistant to downregulation by the CTL. These results imply the existence of CTL-inducible hepatocellular factors that interact with a discrete element(s) between nucleotides 3157 and 1239 within the viral pregenomic and envelope transcripts and mediate their degradation, thus converting the hepatocyte from a passive victim to an active participant in the host response to HBV infection.
Tsui
L V
LV
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Guidotti
L G
LG
Ishikawa
T
T
Chisari
F V
FV
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D003433:Crosses, Genetic; D005260:Female; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D007700:Kinetics; D008099:Liver / Q000276:immunology* / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012367:RNA, Viral / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014158:Transcription, Genetic; D014779:Virus Replication
D012367:RNA, Viral