Related Experiment Video
Updated: Jun 20, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Lethal model for respiratory syncytial virus infection using C57BL/6 mice
Tatsuki Takahashi1, Sodbayasgalan Amarbayasgalan1, Shiori Ueno1
1Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Maebashi-shi, Gunma, Japan.
Abstract:
Respiratory syncytial virus (RSV) infection is a major infectious disease affecting public health. Infants and elderly infected with RSV can develop severe respiratory symptoms. A mouse model mimicking human RSV infection could be useful in elucidating the pathogenesis of RSV. However, previous mouse models did not adequately mimic the pathophysiology of human patients. We attempted to establish a new mouse-adapted RSV strain via serial passaging of mice. We rescued the MP11 virus (which had one non-synonymous substitution in each of the F, G, and L genes) through serial passaging in mice. The MP11 virus was inoculated into mice to evaluate whether it had adapted to the mouse. Viral RNA levels in the lungs of 25-week-old mice infected with MP11 virus were higher than those in the lungs of mice infected with A2 virus. There was a high infiltration of inflammatory cells and high expression of several inflammatory cytokines (IFN-γ, CCL2, TNF-α, and IL-6) in the MP11 virus-infected lungs. Furthermore, the MP11 virus can also cause lethal pneumonia in mice via high-concentration inoculation. These results indicated that the MP11 virus is a more mouse-adapted strain than the A2 virus. We generated a recombinant MP11 virus (rMP11) using reverse genetics. The rMP11 virus could grow in the lungs of mice, similar to the parent MP11 virus. In conclusion, we successfully established a new mouse-adapted strain, MP11, and reverse genetics for this strain. These MP11 and rMP11 viruses could contribute to mouse experiments aimed at elucidating RSV pathogenesis.
Importance:
A mouse model of respiratory syncytial virus (RSV) infection is useful for fundamental research aimed at developing antiviral drugs. Previous mouse models of RSV infection were unable to adequately mimic the pathophysiology of human patients due to the low amplification efficiency of this virus in the mouse lung. Furthermore, mice other than BALB/C mice are difficult to use for the RSV infectious model. We established a new mouse-adapted RSV strain, MP11. The MP11 virus can cause severe pneumonia in C57BL/6 mice and efficiently replicate and induce inflammation in the lung. Therefore, C57BL/6 mice can be used for RSV infection experiments using MP11 virus. We established a reverse genetics system for the MP11 virus using our mouse model. This system enables detailed analyses of the MP11 virus, such as functional analysis of each viral protein. Our study provides techniques that can advance fundamental research in elucidating the pathogenesis of RSV infections.
Insights
Researchers developed a new mouse-adapted respiratory syncytial virus (RSV) strain, MP11, which better mimics human RSV infection in mice. This advancement aids in studying RSV pathogenesis and developing new antiviral treatments.
Area of Science:
- Virology
- Immunology
- Pathogenesis research
Background:
- Respiratory syncytial virus (RSV) poses a significant public health threat, particularly to infants and the elderly.
- Existing mouse models inadequately replicate human RSV pathophysiology due to low viral amplification in mouse lungs.
- Previous models were limited to specific mouse strains like BALB/C, hindering broader research.
Purpose of the Study:
- To establish a novel mouse-adapted RSV strain for improved preclinical studies.
- To develop a robust mouse model for investigating RSV pathogenesis and evaluating antiviral therapies.
- To create a reverse genetics system for the new RSV strain to facilitate detailed viral analysis.
Main Methods:
- Serial passaging of a wild-type RSV strain in mice to generate a mouse-adapted variant (MP11).
- Inoculation of MP11 into C57BL/6 mice to assess viral replication, inflammatory responses, and pathogenicity.
- Generation of a recombinant MP11 virus (rMP11) using reverse genetics.
Main Results:
- The MP11 strain demonstrated higher viral RNA levels in mouse lungs compared to the A2 strain.
- MP11 infection induced significant inflammatory cell infiltration and elevated cytokine expression (IFN-γ, CCL2, TNF-α, IL-6) in lungs.
- MP11 caused lethal pneumonia in mice and showed efficient replication and inflammation induction in C57BL/6 mice.
- A functional reverse genetics system was established for the rMP11 strain.
Conclusions:
- A new, mouse-adapted RSV strain (MP11) and its corresponding reverse genetics system have been successfully developed.
- The MP11 strain effectively replicates in and induces inflammation in C57BL/6 mouse lungs, establishing it as a superior model for RSV research.
- These tools will significantly advance fundamental research into RSV pathogenesis and the development of novel antiviral interventions.
