Defective interfering virus protects elderly mice from influenza

• Published in: Virology journal Vol. 8; no. 1; p. 212
• Main Authors: Scott, Paul D, Meng, Bo, Marriott, Anthony C, Easton, Andrew J, Dimmock, Nigel J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.05.2011; BioMed Central; BMC
• Subjects: Animals; Body Weight; Defective Viruses; defective-interfering virus; Disease Models, Animal; elderly; Female; Genetic aspects; geriatric; Health aspects; Immunity, Innate; influenza; Influenza A virus - immunology; Influenza A virus - pathogenicity; Influenza B virus - immunology; Influenza B virus - pathogenicity; Influenza viruses; Interferons - immunology; Male; Mice; Mice, Inbred C3H; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Rodent Diseases - immunology; Rodent Diseases - pathology; Rodent Diseases - prevention & control; Rodent Diseases - virology; Severity of Illness Index; treatment; Virus Replication; United Kingdom
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-8-212

We have identified and characterised a defective-interfering (DI) influenza A virus particles containing a highly deleted segment 1 RNA that has broad-spectrum antiviral activity. In young adult mice it exerts protection against several different subtypes of influenza A virus (defined here as homologous or genetically compatible protection) and against a paramyxovirus and an influenza B virus (heterologous or genetically unrelated protection). Homologous protection is mediated by replication competition between the deleted and full-length genomes, and heterologous protection occurs through stimulation of innate immunity, especially interferon type I. A single dose of the protective DI virus was administered intranasally to elderly mice at -7, -1 and +1 days relative to intranasal challenge with influenza A virus. A single dose of the DI virus given 1 or 7 days protected elderly mice, reducing a severe, sometimes fatal disease to a subclinical or mild infection. In contrast, all members of control groups treated with inactivated DI virus before challenge became extremely ill and most died. Despite the subclinical/mild nature of their infection, protected mice developed solid immunity to a second infectious challenge. The defective interfering virus is effective in preventing severe influenza A in elderly mice and may offer a new approach to protection of the human population.