Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus

• Published in: Journal of general virology Vol. 92; no. 9; pp. 2122 - 2132
• Main Authors: Scott, Paul D, Meng, Bo, Marriott, Anthony C, Easton, Andrew J, Dimmock, Nigel J
• Format: Journal Article
• Language: English
• Published: Reading Society for General Microbiology 01.09.2011
• Subjects: Animals; Biological and medical sciences; cell culture; Cross Protection; Defective Viruses - immunology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; genome; humans; Immunity, Innate; influenza; Influenza A virus - immunology; Influenza B virus; Influenza B virus - immunology; innate immunity; Interferon Type I - immunology; interferons; intranasal administration; Male; mechanism of action; Mice; Microbiology; Miscellaneous; Orthomyxoviridae Infections - prevention & control; Paramyxoviridae; pathogens; progeny; Rodent Diseases - prevention & control; Virology; viruses; Virus; Orthomyxoviridae; Influenzavirus A; Influenza A virus
• ISSN: 1465-2099; 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.034132-0

Influenza A and B viruses are major human respiratory pathogens that contribute to the burden of seasonal influenza. They are both members of the family Orthomyxoviridae but do not interact genetically and are classified in different genera. Defective interfering (DI) influenza viruses have a major deletion of one or more of their eight genome segments, which renders them both non-infectious and able to interfere in cell culture with the production of infectious progeny by a genetically compatible, homologous virus. It has been shown previously that intranasal administration of a cloned DI influenza A virus, 244/PR8, protects mice from various homologous influenza A virus subtypes and that it also protects mice from respiratory disease caused by a heterologous virus belonging to the family PARAMYXOVIRIDAE: The mechanisms of action in vivo differ, with homologous and heterologous protection being mediated by probable genome competition and type I interferon (IFN), respectively. In the current study, it was shown that 244/PR8 also protects against disease caused by a heterologous influenza B virus (B/Lee/40). Protection from B/Lee/40 challenge was partially eliminated in mice that did not express a functional type I IFN receptor, suggesting that innate immunity, and type I IFN in particular, are important in mediating protection against this virus. It was concluded that 244/PR8 has the ability to protect in vivo against heterologous IFN-sensitive respiratory viruses, in addition to homologous influenza A viruses, and that it acts by fundamentally different mechanisms.