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An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells.
Lulla, Valeria; Dinan, Adam M; Hosmillo, Myra; Chaudhry, Yasmin; Sherry, Lee; Irigoyen, Nerea; Nayak, Komal M; Stonehouse, Nicola J; Zilbauer, Matthias; Goodfellow, Ian; Firth, Andrew E.
Afiliação
  • Lulla V; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. vl284@cam.ac.uk.
  • Dinan AM; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Hosmillo M; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Chaudhry Y; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Sherry L; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.
  • Irigoyen N; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Nayak KM; Department of Paediatrics, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Stonehouse NJ; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.
  • Zilbauer M; Department of Paediatrics, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Goodfellow I; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
  • Firth AE; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. aef24@cam.ac.uk.
Nat Microbiol ; 4(2): 280-292, 2019 02.
Article em En | MEDLINE | ID: mdl-30478287
Enteroviruses comprise a large group of mammalian pathogens that includes poliovirus. Pathology in humans ranges from sub-clinical to acute flaccid paralysis, myocarditis and meningitis. Until now, all of the enteroviral proteins were thought to derive from the proteolytic processing of a polyprotein encoded in a single open reading frame. Here we report that many enterovirus genomes also harbour an upstream open reading frame (uORF) that is subject to strong purifying selection. Using echovirus 7 and poliovirus 1, we confirmed the expression of uORF protein in infected cells. Through ribosome profiling (a technique for the global footprinting of translating ribosomes), we also demonstrated translation of the uORF in representative members of the predominant human enterovirus species, namely Enterovirus A, B and C. In differentiated human intestinal organoids, uORF protein-knockout echoviruses are attenuated compared to the wild-type at late stages of infection where membrane-associated uORF protein facilitates virus release. Thus, we have identified a previously unknown enterovirus protein that facilitates virus growth in gut epithelial cells-the site of initial viral invasion into susceptible hosts. These findings overturn the 50-year-old dogma that enteroviruses use a single-polyprotein gene expression strategy and have important implications for the understanding of enterovirus pathogenesis.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Virais / Fases de Leitura Aberta / Enterovirus / Infecções por Enterovirus / Mucosa Intestinal Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Virais / Fases de Leitura Aberta / Enterovirus / Infecções por Enterovirus / Mucosa Intestinal Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article