Molecular dissection of HBV evasion from restriction factor tetherin: A new perspective for antiviral cell therapy

Oncotarget
Kei MiyakawaAkihide Ryo

Abstract

Viruses have evolved various strategies to escape from the innate cellular mechanisms inhibiting viral replication and spread. Extensive evidence has highlighted the ineffectiveness of interferon (IFN) therapy against chronic hepatitis B virus (HBV) infection, implying the existence of mechanisms by which HBV evades IFN-induced antiviral responses. In our current study, we demonstrate that HBV surface protein (HBs) plays a crucial role in counteracting the IFN-induced antiviral response mediated by tetherin (also known as BST-2). The type I IFN treatment of HBV-producing cells marginally but significantly inhibited the release of HBsAg and viral DNA, but this release was recovered by the knockdown of tetherin. HBs can interact with tetherin via its fourth 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 (iPSC)-derived hepatocytes. Our current results thus reveal a previously undescribed molecular link between HBV and tetherin durin...Continue Reading

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Citations

Feb 2, 2019·Reviews in Medical Virology·Anshika Sharma, Sunil K Lal
Apr 25, 2019·Nature Communications·Kei MiyakawaAkihide Ryo
Sep 27, 2019·Journal of Medical Virology·Baisong ZhengWenyan Zhang
May 28, 2016·Scientific Reports·Andreas F R SommerRenate König
Jan 18, 2018·Viruses·Shuliang ChenDeyin Guo
Apr 5, 2016·Immunity, Inflammation and Disease·Wadie D Mahauad-Fernandez, Chioma M Okeoma
Sep 2, 2017·Vaccines·Ana Maria Ortega-Prieto, Marcus Dorner
Feb 23, 2020·Frontiers in Cell and Developmental Biology·Mayuko NishiAkihide Ryo
Apr 19, 2020·International Immunopharmacology·Abdullah Al MamunJian Xiao
May 25, 2021·Frontiers in Immunology·Ravesh SinghThumbi Ndung'u

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Methods Mentioned

BETA
PCR
ELISA
confocal microscopy
pull-down
immunoprecipitation
transfection

Software Mentioned

Prism
GraphPad
NIH ImageJ

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