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Activation of Pattern Recognition Receptor-Mediated Innate Immunity Inhibits the Replication of Hepatitis B Virus in Human Hepatocyte-Derived Cells
Journal article   Open access   Peer reviewed

Activation of Pattern Recognition Receptor-Mediated Innate Immunity Inhibits the Replication of Hepatitis B Virus in Human Hepatocyte-Derived Cells

Haitao Guo, Dong Jiang, Dongling Ma, Jinhong Chang, Anne Marie Dougherty, Andrea Cuconati, Timothy M. Block and Ju-Tao Guo
Journal of virology, v 83(2), pp 847-858
29 Oct 2008
DOI: https://doi.org/10.1128/JVI.02008-08
PMID: 18971270
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/jvi.02008-08View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Genome and Regulation of Viral Gene Expression
Recognition of virus infections by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I), and melanoma differentiation associated gene 5 (MDA5), activates signaling pathways, leading to the induction of inflammatory cytokines that limit viral replication. To determine the effects of PRR-mediated innate immune response on hepatitis B virus (HBV) replication, a 1.3mer HBV genome was cotransfected into HepG2 or Huh7 cells with plasmid expressing TLR adaptors, myeloid differentiation primary response gene 88 (MyD88), and TIR-domain-containing adaptor-inducing beta interferon (TRIF), or RIG-I/MDA5 adaptor, interferon promoter stimulator 1 (IPS-1). The results showed that expressing each of the three adaptors dramatically reduced the levels of HBV mRNA and DNA in both HepG2 and Huh7 cells. However, HBV replication was not significantly affected by treatment of HBV genome-transfected cells with culture media harvested from cells transfected with each of the three adaptors, indicating that the adaptor-induced antiviral response was predominantly mediated by intracellular factors rather than by secreted cytokines. Analyses of involved signaling pathways revealed that activation of NF-κB is required for all three adaptors to elicit antiviral response in both HepG2 and Huh7 cells. However, activation of interferon regulatory factor 3 is only essential for induction of antiviral response by IPS-1 in Huh7 cells, but not in HepG2 cells. Furthermore, our results suggest that besides NF-κB, additional signaling pathway(s) are required for TRIF to induce a maximum antiviral response against HBV. Knowing the molecular mechanisms by which PRR-mediated innate defense responses control HBV infections could potentially lead to the development of novel therapeutics that evoke the host cellular innate antiviral response to control HBV infections.

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Web of Science research areas
Virology
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