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Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles.
Ding, Qiang; Heller, Brigitte; Capuccino, Juan M V; Song, Bokai; Nimgaonkar, Ila; Hrebikova, Gabriela; Contreras, Jorge E; Ploss, Alexander.
Afiliação
  • Ding Q; Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544.
  • Heller B; Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544.
  • Capuccino JM; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, Newark, NJ 07103.
  • Song B; Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544.
  • Nimgaonkar I; Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544.
  • Hrebikova G; Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544.
  • Contreras JE; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, Newark, NJ 07103.
  • Ploss A; Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544; aploss@princeton.edu.
Proc Natl Acad Sci U S A ; 114(5): 1147-1152, 2017 01 31.
Article em En | MEDLINE | ID: mdl-28096411
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.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Proteínas Virais / Vírus da Hepatite E / Liberação de Vírus / Canais Iônicos Limite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Proteínas Virais / Vírus da Hepatite E / Liberação de Vírus / Canais Iônicos Limite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2017 Tipo de documento: Article