Type I interferon signaling protects mice from lethal henipavirus infection.

Hendra virus (HeV) and Nipah virus (NiV) are closely related, recently emerged paramyxoviruses that form Henipavirus genus and are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. However, in contrast to many other species and despite expression of functional virus entry receptors, mice are resistant to henipavirus infection. We report here the susceptibility of mice deleted for the type I interferon receptor (IFNAR-KO) to both HeV and NiV. Intraperitoneally infected mice developed fatal encephalitis, with pathology and immunohistochemical features similar to what was found in humans. Viral RNA was found in the majority of analyzed organs, and sublethally infected animals developed virus-specific neutralizing antibodies. Altogether, these results reveal IFNAR-KO mice as a new small animal model to study HeV and NiV pathogenesis, prophylaxis, and treatment and suggest the critical role of type I interferon signaling in the control of henipavirus infection.
AuthorsKévin P Dhondt, Cyrille Mathieu, Marie Chalons, Joséphine M Reynaud, Audrey Vallve, Hervé Raoul, Branka Horvat
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 1 Pg. 142-51 (Jan 1 2013) ISSN: 1537-6613 [Electronic] United States
PMID23089589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Interferon Type I
  • RNA, Viral
  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral (immunology)
  • Antibody Specificity
  • Brain (virology)
  • Cells, Cultured
  • Disease Models, Animal
  • Encephalitis, Viral (immunology, mortality, prevention & control, virology)
  • Hendra Virus (genetics, immunology, pathogenicity)
  • Henipavirus (genetics, immunology, pathogenicity)
  • Henipavirus Infections (immunology, mortality, prevention & control, virology)
  • Humans
  • Interferon Type I (genetics, immunology)
  • Mice
  • Mice, Knockout
  • Neuroglia (virology)
  • Nipah Virus (genetics, immunology, pathogenicity)
  • RNA, Viral (analysis)
  • Signal Transduction
  • Survival Analysis
  • Virulence
  • Virus Internalization
  • Virus Replication

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