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Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles

Author(s): Ding, Qiang; Heller, Brigitte; Capuccino, Juan MV; Song, Bokai; Nimgaonkar, Ila; et al

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Abstract: Hepatitis E virus (HEV) is the leading cause of enterically transmitted viral hepatitis globally. Of HEV’s three ORFs, the function of ORF3 has remained elusive. Here, we demonstrate that via homophilic interactions ORF3 forms multimeric complexes associated with intracellular endoplasmic reticulum (ER)-derived membranes. HEV ORF3 shares several structural features with class I viroporins, and the function of HEV ORF3 can be maintained by replacing it with the well-characterized viroporin influenza A virus (IAV) matrix-2 protein. ORF3’s ion channel function is further evidenced by its ability to mediate ionic currents when expressed in Xenopus laevis oocytes. Furthermore, we identified several positions in ORF3 critical for its formation of multimeric complexes, ion channel activity, and, ultimately, release of infectious particles. Collectively, our data demonstrate a previously undescribed function of HEV ORF3 as a viroporin, which may serve as an attractive target in developing direct-acting antivirals
Publication Date: 31-Jan-2017
Electronic Publication Date: 17-Jan-2017
Citation: Ding, Qiang, Heller, Brigitte, Capuccino, Juan MV, Song, Bokai, Nimgaonkar, Ila, Hrebikova, Gabriela, Contreras, Jorge E, Ploss, Alexander. (2017). Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles. Proceedings of the National Academy of Sciences, 114 (5), 1147 - 1152. doi:10.1073/pnas.1614955114
DOI: doi:10.1073/pnas.1614955114
ISSN: 0027-8424
EISSN: 1091-6490
Pages: 1147 - 1152
Type of Material: Journal Article
Journal/Proceeding Title: Proceedings of the National Academy of Sciences
Version: Final published version. Article is made available in OAR by the publisher's permission or policy.

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