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Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
Published on: June 24, 2012
Interferon lambda (IFN-λ) efficiently blocks norovirus transmission in a mouse model
Joana Rocha-Pereira1, Sophie Jacobs2, Sam Noppen1
1KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Abstract:
Human noroviruses are highly efficient in person to person transmission thus associated with explosive outbreaks of acute gastroenteritis. Outbreak control is limited to disinfection and isolation measures. Strategies to control the spread of noroviruses should be developed and models to study norovirus transmission will greatly facilitate this. Here, a mouse-to-mouse transmission model, in which mice develop acute murine norovirus (MNV)-induced diarrhea, was used to explore the role of interferon lambda (IFN-λ) in the control of a norovirus infection. Sentinel AG129 mice [deficient in IFN-α/β and IFN-γ receptors] that were co-housed with MNV-infected mice shedding high amounts of virus in their stool, developed a MNV-infection with associated diarrhea. Inoculation of such sentinel mice with an IFN-λ expression plasmid resulted in the production of circulating IFN-λ and upregulation of the expression of IFN-stimulated genes (ISGs) of the gut. Injection of the IFN-λ-expressing plasmid to sentinels prevents MNV-induced disease upon exposure to MNV-infected mice, as well as MNV replication in the small intestine, the associated signs of inflammation and the mounting of a specific IgG-based immune response. This demonstrates that IFN-λ can alone mediate protection against transmission of norovirus. The development of a simple delivery method for IFN-λ could be explored as a strategy to control norovirus outbreaks and protect vulnerable populations such as the elderly and immunocompromised.
Insights
Interferon lambda (IFN-λ) administration prevents norovirus transmission and disease in mice. This discovery offers a potential new strategy for controlling norovirus outbreaks and protecting vulnerable populations.
Area of Science:
- Immunology
- Virology
- Gastroenterology
Background:
- Human noroviruses cause widespread gastroenteritis outbreaks due to efficient person-to-person transmission.
- Current norovirus outbreak control relies on disinfection and isolation, highlighting the need for novel strategies.
- Developing models to study norovirus transmission is crucial for advancing control measures.
Purpose of the Study:
- To investigate the role of interferon lambda (IFN-λ) in controlling norovirus infection using a mouse model.
- To assess the protective potential of IFN-λ against murine norovirus (MNV) transmission and disease.
Main Methods:
- A mouse-to-mouse transmission model was established using MNV-infected mice and sentinel AG129 mice (deficient in IFN-α/β and IFN-γ receptors).
- Sentinel mice received an IFN-λ expression plasmid, leading to circulating IFN-λ and gut IFN-stimulated gene (ISG) expression.
- Protection against MNV-induced disease, replication, inflammation, and immune response was evaluated post-exposure.
Main Results:
- Sentinel mice exposed to MNV-infected littermates developed MNV infection and diarrhea.
- IFN-λ administration prevented MNV-induced disease, suppressed viral replication in the small intestine, and reduced inflammation.
- IFN-λ treatment also inhibited the development of a specific IgG-based immune response to MNV.
Conclusions:
- Interferon lambda (IFN-λ) alone can confer protection against norovirus transmission.
- IFN-λ administration effectively controls MNV infection and associated pathology in a susceptible mouse model.
- Developing simple IFN-λ delivery methods could offer a novel strategy for norovirus outbreak control and protection of at-risk groups.

