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

Vaccine. 2011 Mar 24;29(15):2777-84. doi: 10.1016/j.vaccine.2011.01.102. Epub 2011 Feb 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Defective Viruses / genetics
  • Defective Viruses / immunology*
  • Humans
  • Influenza A virus / genetics
  • Influenza A virus / immunology*
  • Interferon Type I / immunology
  • Mice
  • Murine pneumonia virus / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Pneumovirus Infections / prevention & control*
  • Respiratory Tract Infections / prevention & control*
  • Survival Analysis


  • Interferon Type I