Pathogenic difference of respiratory syncytial virus infection in cotton rats of different ages

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections globally.
• Disease severity in infants and the elderly is linked to immature or declining immunity, but pathogenesis differences are understudied.
• The cotton rat is a susceptible model for RSV infection.

Purpose of the Study:

• To establish and characterize an age-dependent RSV infection model in cotton rats (infant, adult, elderly).
• To investigate age-related differences in RSV pathogenesis, viral load, and immune responses.
• To provide a model for developing age-specific RSV vaccines and treatments.

Main Methods:

• Established RSV infection models in 3-week (infant), 8-week (adult), and 30-week (elderly) old cotton rats.
• Administered a standardized dose of RSV to all age groups.
• Assessed viral load, airway inflammation (neutrophil infiltration), immune markers (IFN-α, Mx2, TNF-α), mucus production, and pathology.

Main Results:

• Infant (3-week) rats showed higher viral loads, potentially due to lower IFN-α/Mx2 levels.
• Adult (8-week) rats exhibited significant pulmonary inflammation and peribronchiolitis despite adequate IFN-α/Mx2.
• Elderly (30-week) rats displayed the most severe pathology, delayed viral clearance, increased mucus, and altered IFN-α response.

Conclusions:

• Cotton rat models demonstrate age-dependent RSV disease severity and immune responses.
• Findings highlight distinct pathogenic mechanisms across different age groups in this model.
• This age-stratified cotton rat model can inform personalized RSV vaccine development and targeted therapies.