title: A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral.
abstract: Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.
authors.affiliation: Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. c.m.smith@ucl.ac.uk.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Smith
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. paul.scott14@nhs.net.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Scott
authors.affiliation: Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. c.ocallaghan@ucl.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Callaghan
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. a.j.easton@warwick.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Easton
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. n.j.dimmock@warwick.ac.uk.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Dimmock
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000378:metabolism*; D003673:Defective Viruses / Q000235:genetics*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology*; D005289:Ferrets; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012367:RNA, Viral / Q000008:administration & dosage / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral
keywords: antiviral; defective interfering; human respiratory cells; influenza virus