Lethal model for respiratory syncytial virus infection using C57BL/6 mice

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.