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Posttranscriptional clearance of hepatitis B virus RNA by cytotoxic T lymphocyte-activated hepatocytes

Academic Article
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Overview

authors

  • Tsui, L. V.
  • Guidotti, Luca
  • Ishikawa, T.
  • Chisari, Francis

publication date

  • December 1995

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • 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.

subject areas

  • Animals
  • Blotting, Northern
  • Cell Nucleus
  • Crosses, Genetic
  • Female
  • Genome, Viral
  • Hepatitis B virus
  • Kinetics
  • Liver
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Transgenic
  • RNA, Viral
  • T-Lymphocytes, Cytotoxic
  • Transcription, Genetic
  • Virus Replication
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Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.92.26.12398

PubMed ID

  • 8618909
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Additional Document Info

start page

  • 12398

end page

  • 12402

volume

  • 92

issue

  • 26

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