Hepatitis B virus persistence in mice reveals IL-21 and IL-33 as regulators of viral clearance

Zhongliang Shen, Huijuan Yang, Sisi Yang, Wei Wang, Xiaoxian Cui, Xian Zhou, Wei Liu, Shaokun Pan, Yanfeng Liu, Junqi Zhang, Jiming Zhang (), Youhua Xie () and Jing Liu ()
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Zhongliang Shen: Fudan University
Huijuan Yang: Fudan University
Sisi Yang: Huashan Hospital, Fudan University
Wei Wang: Fudan University
Xiaoxian Cui: Fudan University
Xian Zhou: Fudan University
Wei Liu: Fudan University
Shaokun Pan: Fudan University
Yanfeng Liu: Fudan University
Junqi Zhang: Fudan University
Jiming Zhang: Fudan University
Youhua Xie: Fudan University
Jing Liu: Fudan University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Hepatitis B virus (HBV) generally causes self-limiting infection in immunocompetent adults, but establishes chronic infection in some adults and in most maternally infected infants. Factors determining clearance versus persistence are not fully understood. Hydrodynamic injection (HDI) of HBV replicon plasmid via tail vein generally results in quick clearance in immunocompetent adult mice. Here, we report the identification of strain-specific persistence of HBV in mice: one genotype B strain, designated BPS, persisted up to 33 weeks in ~50% of HDI mice. BPS persistence requires viral replication and multiple viral features. Compared to quickly cleared strains, BPS fails to induce robust post-exposure serum IL-21/IL-33 responses. Injection of IL-21-expressing or IL-33-expressing plasmids facilitates clearance of pre-established BPS persistence and protects cured mice from BPS re-challenge. IL-21 and IL-33 also induce clearance of pre-established HBV persistence in another mouse model. These data reveal IL-21 and IL-33 as potent regulators of HBV clearance and valid drug candidates.

Date: 2017
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DOI: 10.1038/s41467-017-02304-7

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