A Genome-wide CRISPR Screen Identifies ZCCHC14 as a Host Factor Required for Hepatitis B Surface Antigen Production | Zendy

Anastasia Hyrina | Zendy; Christopher T. Jones | Zendy; Darlene Chen | Zendy; Scott Clarkson | Zendy; Nadire R. Cochran | Zendy; Paul Feucht | Zendy; Gregory R. Hoffman | Zendy; Alicia Lindeman | Zendy; Carsten Russ | Zendy; Frederic Sigoillot | Zendy; Tiffany Tsang | Zendy; Kyoko Uehara | Zendy; Lili Xie | Zendy; Don Ganem | Zendy; Meghan Holdorf | Zendy

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A Genome-wide CRISPR Screen Identifies ZCCHC14 as a Host Factor Required for Hepatitis B Surface Antigen Production

Author(s) -

Anastasia Hyrina,

Christopher T. Jones,

Darlene Chen,

Scott Clarkson,

Nadire R. Cochran,

Paul Feucht,

Gregory R. Hoffman,

Alicia Lindeman,

Carsten Russ,

Frederic Sigoillot,

Tiffany Tsang,

Kyoko Uehara,

Lili Xie,

Don Ganem,

Meghan Holdorf

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.10.113

Subject(s) - hbsag , crispr , biology , zinc finger , virology , gene , genome editing , hepatitis b virus , rna , antigen , genome , host factor , computational biology , virus , immunology , genetics , transcription factor

A hallmark of chronic hepatitis B (CHB) virus infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A small molecule, RG7834, has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase proteins 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identify additional factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients.

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