A MAVS/TICAM-1-independent interferon-inducing pathway contributes to regulation of hepatitis B virus replication in the mouse hydrodynamic injection model.

Abstract

Toll-like receptors (TLRs) and cytoplasmic RNA sensors have been reported to be involved in the regulation of hepatitis B virus (HBV) replication, but remain controversial due to the lack of a natural infectious model. Our current study sets out to characterize aspects of the role of the innate immune system in eliminating HBV using hydrodynamic-based injection of HBV replicative plasmid and knockout mice deficient in specific pathways of the innate system. The evidence indicated that viral replication was not affected by MAVS or TICAM-1 knockout, but absence of interferon regulatory factor 3 (IRF-3) and IRF-7 transcription factors, as well as the interferon (IFN) receptor, had an adverse effect on the inhibition of HBV replication, demonstrating the dispensability of MAVS and TICAM-1 pathways in the early innate response against HBV. Myd88(-/-) mice did not have a significant increase in the initial viremia, but substantial viral antigen persisted in the mice sera, a response similar to Rag2(-/-) mice, suggesting that the MyD88-dependent pathway participated in evoking an adaptive immune response against the clearance of intrahepatic HBV. Taken together, we show that the RNA-sensing pathways do not participate in the regulation of HBV replication in a mouse model; meanwhile MyD88 is implicated in the HBV clearance.

• Authors: Chean Ring Leong, Hiroyuki Oshiumi, Masaaki Okamoto, Masahiro Azuma, Hiromi Takaki, Misako Matsumoto, Kazuaki Chayama, Tsukasa Seya
• Journal: Journal of innate immunity (J Innate Immun) Vol. 7 Issue 1 Pg. 47-58 ( 2015) ISSN: 1662-8128 [Electronic] Switzerland
• PMID: 25115498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Hepatitis B Antigens
• IPS-1 protein, mouse
• Interferon Regulatory Factor-3
• Interferon Regulatory Factor-7
• Irf3 protein, mouse
• Irf7 protein, mouse
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• TICAM-1 protein, mouse

Topics

• Adaptor Proteins, Signal Transducing (genetics, immunology)
• Adaptor Proteins, Vesicular Transport (genetics, immunology)
• Animals
• Disease Models, Animal
• Hepatitis B (genetics, immunology)
• Hepatitis B Antigens (genetics, immunology)
• Hepatitis B virus (physiology)
• Interferon Regulatory Factor-3 (genetics, immunology)
• Interferon Regulatory Factor-7 (genetics, immunology)
• Mice
• Mice, Knockout
• Myeloid Differentiation Factor 88 (genetics, immunology)
• Signal Transduction (genetics, immunology)
• Virus Replication (immunology)