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Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200

1
College of Life Sciences, Wuhan University, Wuhan 430072, China
2
Structural Studies Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK
3
Department of Clinical Laboratory, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(5), 427; https://doi.org/10.3390/v11050427
Received: 17 March 2019 / Revised: 4 May 2019 / Accepted: 7 May 2019 / Published: 9 May 2019
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

Human hepatitis B virus core protein (HBc) is a structural protein of the hepatitis B virus (HBV) and contributes to HBV regulation of host-cell transcription. However, the mechanisms of transcriptional regulation remain poorly characterized. To dissect the function of HBc, a yeast two-hybrid was performed to identify HBc-binding proteins, and the C-terminal of BRG1/hBRM-associated factors 200 (BAF200C) was identified. Then, the existence of HBc interactions with BAF200C and full-length BAF200 was confirmed via co-immunoprecipitation assays in 293T, HepG2 and HepG2-NTCP cells. Furthermore, we show that the binding between HBc and BAF200 was of vital importance to HBc mediated downregulation of interferon-induced transmembrane protein 1 (IFITM1) expression, and the mechanisms for the downregulation were disclosed as follows. Basal level of IFITM1 expression depends on BAF200, rather than the JAK–STAT1 pathway. The interaction of HBc with BAF200 disturbs the stability of the polybromo-associated BAF (PBAF) complex and results in the suppression of IFTM1 transcription. Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Collectively, our findings indicate that HBc plays a role in HBV resistance against the antiviral activities of IFNα, providing details about HBV evasion of host innate immunity. View Full-Text
Keywords: Human hepatitis B virus core protein (HBc); BRG1/hBRM-associated factors 200 (BAF200); interferon α (IFNα); interferon-induced transmembrane protein 1 (IFITM1) Human hepatitis B virus core protein (HBc); BRG1/hBRM-associated factors 200 (BAF200); interferon α (IFNα); interferon-induced transmembrane protein 1 (IFITM1)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Li, T.; Ke, Z.; Liu, W.; Xiong, Y.; Zhu, Y.; Liu, Y. Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200. Viruses 2019, 11, 427.

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