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Published on: June 14, 2020
Nipah virus Malaysia and Bangladesh strain-induced pathogenesis in mice lacking type I interferon receptor signaling
Lucia Amurri1, Olivier Reynard1, Ilona Ronco1
1CIRI, Centre International de Recherche en Infectiologie, INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon, Lyon, France.
Abstract:
Nipah virus (NiV) is a zoonotic highly pathogenic Paramyxovirus inducing lethal outbreaks of encephalitis and Acute Respiratory Distress Syndrome (ARDS) with an average case-fatality rate of 75%. Two viral strains, NiV-Malaysia (NiV-Mal) and NiV-Bangladesh (NiV-Ban), associated to distinct route of transmission, symptoms and lethality have been described. Due to the permanent threat of these emerging infections and the lack of approved therapeutics, it is crucial to improve our understanding regarding NiV-associated pathogenesis. Mice represent a small and accessible animal model, provided with numerous biological tools for the functional assessment of different genes related to antiviral response. Here, we explore the susceptibility of mice deficient for type I interferon receptor (IFNAR KO) to inoculation with either NiV-Mal or NiV-Ban through intraperitoneal or intranasal routes. Our results complement observations showing that IFNAR KO mice are susceptible to NiV-Ban infection via intraperitoneal route, although to a lesser extent than NiV-Mal, and develop encephalitis and a pulmonary syndrome with viral dissemination to various organs. Additionally, intranasal administration of both viral strains exhibited a subclinical infection with viral replication in the brain and the lungs along to the production of neutralizing antibodies in some animals. These results suggest that IFNAR KO mice may represent a reliable model permitting comparative studies of the immunopathogenesis induced by both NiV-Mal and NiV-Ban infections.
Insights
Nipah virus (NiV) infection outcomes were studied in type I interferon receptor-deficient (IFNAR KO) mice. These mice showed susceptibility to NiV strains, suggesting a potential model for comparative Nipah virus pathogenesis research.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Nipah virus (NiV) is a highly pathogenic zoonotic virus causing severe encephalitis and Acute Respiratory Distress Syndrome (ARDS).
- Two main strains, NiV-Malaysia (NiV-Mal) and NiV-Bangladesh (NiV-Ban), exhibit different transmission routes, symptoms, and lethality.
- Lack of approved therapeutics necessitates further understanding of NiV pathogenesis.
Purpose of the Study:
- To investigate the susceptibility of type I interferon receptor knockout (IFNAR KO) mice to NiV-Mal and NiV-Ban infections.
- To evaluate the impact of different inoculation routes (intraperitoneal and intranasal) on NiV infection in IFNAR KO mice.
- To assess the potential of IFNAR KO mice as a model for comparative studies of NiV strains' immunopathogenesis.
Main Methods:
- Inoculation of IFNAR KO mice with NiV-Mal and NiV-Ban via intraperitoneal and intranasal routes.
- Monitoring of infection progression, including clinical signs, viral dissemination, and organ involvement.
- Assessment of host antiviral response, including the production of neutralizing antibodies.
Main Results:
- IFNAR KO mice were susceptible to NiV-Ban via intraperitoneal route, though less so than to NiV-Mal, developing encephalitis and pulmonary syndrome.
- Viral dissemination to multiple organs was observed in infected mice.
- Intranasal inoculation with both NiV strains resulted in subclinical infections with viral replication in the brain and lungs, and antibody production in some animals.
Conclusions:
- IFNAR KO mice are susceptible to NiV infection, with varying outcomes depending on the viral strain and route of administration.
- The study highlights the potential of IFNAR KO mice as a valuable model for comparative research on the immunopathogenesis of different NiV strains.
- Further research using this model could aid in developing effective therapeutic strategies against Nipah virus.

