Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Interleukin-2 and alpha/beta interferon down-regulate hepatitis B virus gene expression in vivo by tumor necrosis factor-dependent and -independent pathways

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Guidotti, Luca
  • Guilhot, S.
  • Chisari, Francis

publication date

  • March 1994

journal

  • Journal of Virology  Journal

abstract

  • We have recently reported that administration of recombinant tumor necrosis factor alpha (TNF-alpha) to hepatitis B virus (HBV) transgenic mice reduces the hepatic steady-state content of HBV-specific mRNA by up to 80% in the absence of liver cell injury. In the current study, we analyzed the regulatory effects of several other inflammatory cytokines in the same transgenic model system. Hepatic HBV mRNA content was reduced by up to 90% following administration of a single noncytopathic dose (100,000 U) of interleukin 2 (IL-2). Comparable effects were produced by administration of alpha and beta interferons (IFN-alpha and IFN-beta), but only after multiple injections of at least 500,000 U per mouse. Importantly, the regulatory effect of IL-2 was completely blocked by the prior administration of antibodies to tumor necrosis factor alpha (TNF-alpha), which did not block the effect of IFN-alpha or IFN-beta. In contrast to these observations, recombinant IFN-gamma, IL-1, IL-3, IL-6, TNF-beta, transforming growth factor beta, and granulocyte-monocyte colony-stimulating factor were inactive in this system. These results suggest that selected inflammatory cytokines can down-regulate HBV gene expression in vivo by at least two pathways, one that is dependent on TNF-alpha and another that is not. These results imply that antigen-nonspecific products of the intrahepatic HBV-specific inflammatory response may contribute to viral clearance or persistence during HBV infection.

subject areas

  • Animals
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression Regulation, Viral
  • Hepatitis B virus
  • Interferon-alpha
  • Interferon-beta
  • Interleukin-2
  • Liver
  • Mice
  • Mice, Transgenic
  • RNA, Messenger
  • RNA, Viral
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
scroll to property group menus

Identity

PubMed Central ID

  • PMC236579

International Standard Serial Number (ISSN)

  • 0022-538X

PubMed ID

  • 8107192
scroll to property group menus

Additional Document Info

start page

  • 1265

end page

  • 1270

volume

  • 68

issue

  • 3

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support