A novel broad-spectrum treatment for respiratory virus infections: Influenza-based defective interfering virus provides protection against pneumovirus infection in vivo

• Published in: Vaccine Vol. 29; no. 15; pp. 2777 - 2784
• Main Authors: Easton, Andrew J., Scott, Paul D., Edworthy, Nicole L., Meng, Bo, Marriott, Anthony C., Dimmock, Nigel J.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 24.03.2011; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; antiviral agents; Applied microbiology; Biological and medical sciences; Cell culture; Cloning; Defective interfering; Defective Viruses - genetics; Defective Viruses - immunology; Fundamental and applied biological sciences. Psychology; genome; Genomes; Humans; Infections; Influenza; Influenza A virus; Influenza A virus - genetics; Influenza A virus - immunology; innate immunity; Interferon Type I - immunology; interferons; Mice; Microbiology; Miscellaneous; mixed infection; Murine orthopneumovirus; Murine pneumonia virus; Murine pneumonia virus - immunology; mutants; Orthomyxoviridae; Orthomyxoviridae Infections - prevention & control; Paramyxoviridae; Pneumonia virus of mice; Pneumovirus; Pneumovirus Infections - prevention & control; Protection; Respiratory Tract Infections - prevention & control; RNA polymerase; Survival Analysis; vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; Viruses; Defective interfering; Pneumovirus; Protection; Influenza; Pneumovirinae; Respiratory disease; Orthomyxoviridae; Influenzavirus; Paramyxoviridae; Infection; Virus; Mononegavirales; Treatment; Viral disease
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2011.01.102

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 1 μg 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.