Extended protection against influenza A virus by prior rhinovirus infection in a mouse model 9347

Abstract Description Respiratory viral co-infections impact public health through virus interactions that affect disease severity. Clinical observations show rhinovirus (RV) infection can protect against subsequent influenza infection, but the duration and mechanisms of this viral interference are not fully understood. Our previous work demonstrated that RV protects mice from lethal influenza challenge when given 2 days before influenza infection through two mechanisms: RV triggered an early controlled inflammatory response with enhanced immune cell recruitment and higher type I interferon expression promoting faster viral clearance, while limiting immunopathology by reducing neutrophil infiltration. Interferon signaling inhibition eliminated this protection. This study examined the temporal dynamics of RV-induced protection against influenza across infection intervals from 2 to 14 days. We observed significant protection through 14 days, with RV-pre-infected groups showing better survival rates and reduced weight loss and clinical scores compared to controls after influenza A virus infection. This extended protection challenges conventional views of short-lived innate immune responses, as type I interferon typically returns to baseline within two days post-RV infection. This prolonged protection may involve sustained interferon-dependent downstream signaling activation or trained immunity through cellular reprogramming, though further research is needed to identify specific mechanisms. Funding Sources NIH RO1GM152736; NIH/NIGMS: 3P20GM104420-10S2 Topic Categories Viral Immunology (VIR)