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

Luca G. Guidotti, Stephane Guilhot, Francis V. Chisari

Research output: Contribution to journalArticle

Abstract

We have recently reported that administration of recombinant tumor necrosis factor alpha (TNF-α) 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-α and IFN-β), 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-α), which did not block the effect of IFN-α or IFN-β. In contrast to these observations, recombinant IFN-γ, IL-1, IL-3, IL-6, TNF-β, 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-α 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.

Original languageEnglish
Pages (from-to)1265-1270
Number of pages6
JournalJournal of Virology
Volume68
Issue number3
Publication statusPublished - Mar 1994

Fingerprint

interferon-beta
Hepatitis B virus
tumor necrosis factors
Interferon-beta
interleukin-2
Interferon-alpha
Interleukin-2
Down-Regulation
Tumor Necrosis Factor-alpha
Gene Expression
gene expression
tumor necrosis factor-alpha
Liver
cytokines
colony-stimulating factors
genetically modified organisms
interleukin-3
Cytokines
Messenger RNA
liver

ASJC Scopus subject areas

  • Immunology

Cite this

Interleukin-2 and alpha/beta interferon down-regulate hepatitis B virus gene expression in vivo by tumor necrosis factor-dependent and -independent pathways. / Guidotti, Luca G.; Guilhot, Stephane; Chisari, Francis V.

In: Journal of Virology, Vol. 68, No. 3, 03.1994, p. 1265-1270.

Research output: Contribution to journalArticle

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