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

Tongya Li,Ying Zhu,Zunlong Ke,Ying Xiong,Yingle Liu,Weiyong Liu

doi:10.3390/v11050427

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.

Highlights

The human hepatitis B virus (HBV) is a double stranded DNA virus in the Hepadnaviridae family [1].HBV infection could cause acute and chronic Hepatitis B (CHB), which can progress to cirrhosis and hepatocellular carcinoma, leading to high mortality rates worldwide
Since the Janus kinase (JAK)–STAT1 signaling pathway has been reported to be essential to IFNα-induced antiviral activities [26], we examined whether it was involved in BAF200-mediated interferon-induced transmembrane protein 1 (IFITM1) expression
HBV replication is not directly cytotoxic to cells, while the host immune responses in infected hepatocytes are the main of hepatocellular injury and HBV

Summary

Introduction

HBV infection could cause acute and chronic Hepatitis B (CHB), which can progress to cirrhosis and hepatocellular carcinoma, leading to high mortality rates worldwide. Experimental data from HBV infected chimpanzees and urokinase-type plasminogen activator/severe combined immunodeficiency (uPA-SCID) mice have shown that HBV infection does not induce an intrahepatic innate immune response that can be detected [2,3]. This is because early in infection it acts like a stealth virus, remaining undetected and spreading until the onset of the adaptive immune response several weeks later [4]. Besides acting as a Viruses 2019, 11, 427; doi:10.3390/v11050427 www.mdpi.com/journal/viruses

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