title: A novel broad-spectrum treatment for respiratory virus infections: influenza-based defective interfering virus provides protection against pneumovirus infection in vivo.
abstract: Respiratory viruses represent a major clinical burden. Few vaccines and antivirals are available, and the rapid appearance of resistant viruses is a cause for concern. We have developed a novel approach which exploits defective viruses (defective interfering (DI) or protecting viruses). These are naturally occurring deletion mutants which are replication-deficient and multiply only when coinfection with a genetically compatible infectious virus provides missing function(s) in trans. Interference/protection is believed to result primarily from genome competition and is therefore usually confined to the virus from which the DI genome originated. Using intranasally administered protecting influenza A virus we have successfully protected mice from lethal in vivo infection with influenza A viruses from several different subtypes [1]. Here we report, contrary to expectation, that protecting influenza A virus also protects in vivo against a genetically unrelated respiratory virus, pneumonia virus of mice, a pneumovirus from the family Paramyxoviridae. A single dose that contains 1μg of protecting virus protected against lethal infection. This protection is achieved by stimulating type I interferon and possibly other elements of innate immunity. Protecting virus thus has the potential to protect against all interferon-sensitive respiratory viruses and all influenza A viruses.
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.forename: Paul D
authors.initials: PD
authors.lastname: Scott
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Edworthy
authors.forename: Bo
authors.initials: B
authors.lastname: Meng
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Marriott
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology; D051379:Mice; D029122:Murine pneumonia virus / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D018186:Pneumovirus Infections / Q000517:prevention & control*; D012141:Respiratory Tract Infections / Q000517:prevention & control*; D016019:Survival Analysis
chemical_list: D007370:Interferon Type I