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


Journal of Antivirals & Antiretrovirals

Author(s): Guidotti LG, Guilhot S, Chisari FV

Abstract Share this page

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.
This article was published in J Virol and referenced in Journal of Antivirals & Antiretrovirals

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version