Molecular dissection of HBV evasion from host antiviral responses

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860306
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKAWA Kei 横浜市立大学, 医学部, 助教 (20580046)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ウイルス-宿主相互作用 / ピロトーシス

Outline of Final Research Achievements

Accumulating evidence strongly suggests the ineffectiveness of interferon (IFN) therapy against chronic hepatitis B virus (HBV) infection. In this study, we demonstrate that HBV surface protein (HBs) plays a crucial role in counteracting the IFN-induced antiviral response mediated by an antiviral membrane protein tetherin. HBs can interact with tetherin via its transmembrane domain thereby inhibiting its dimerization and antiviral activity. The expression of a tetherin mutant devoid of the HBs-binding domain promoted a prominent restriction of HBV particle production. that eventually resulted in the alleviation of caspase-1-mediated cytotoxicity and interleukin-1β secretion in induced pluripotent stem cell-derived hepatocytes. Our current study thus reveals a previously un-described molecular link between HBV and tetherin during the course of an IFN-induced antiviral response.

Free Research Field

ウイルス学