title: Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral.
abstract: Another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host. This "protecting RNA" (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A 120-ng intranasal dose of this 244 protecting virus completely protected mice against a simultaneous challenge of 10 50% lethal doses with influenza A/WSN (H1N1) virus. The 244 virus also protected mice against strong challenge doses of all other subtypes tested (i.e., H2N2, H3N2, and H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was a clear therapeutic benefit when the 244 virus was administered 24 to 48 h after a lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral, having the potential to combat human influenza virus infections, particularly when the infecting strain is not known or is resistant to antiviral drugs.
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Dimmock
authors.forename: Edward W
authors.initials: EW
authors.lastname: Rainsford
authors.forename: Paul D
authors.initials: PD
authors.lastname: Scott
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Marriott
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002460:Cell Line; D003673:Defective Viruses / Q000502:physiology*; D006378:Helper Viruses / Q000502:physiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology; D053121:Influenza A Virus, H2N2 Subtype / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology; D053123:Influenza A Virus, H3N8 Subtype / Q000502:physiology; D009980:Influenza A virus / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000628:therapy; D010957:Plasmids; D012367:RNA, Viral / Q000032:analysis / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D014162:Transfection; D015431:Weight Loss
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral