Hidden in plain sight: Long-term impacts of respiratory virus infections

Respiratory RNA viruses pose a significant public health challenge by causing life-threatening seasonal infections with long-lasting implications in chronic pulmonary conditions. While infections by respiratory viruses such as parainfluenza virus, respiratory syncytial virus (RSV), rhinoviruses, coronaviruses, and influenza virus were long thought to follow a simple, self-limited course, during my graduate training I discovered that influenza, RSV and rhinoviruses are found associated with immune cells in tonsillar tissues from pediatric patients, in the absence of respiratory symptoms. During my postdoctoral work I used a versatile model of murine respiratory virus infection to prove that despite the apparent viral clearance, innate immune cells are reservoirs for virus persistence in the lungs. These viral-imprinted cells remain in the lower respiratory tract with long-lasting altered transcriptomic footprints, and we discovered that they are critical players to the development of chronic lung pathology. While this was striking evidence of how direct respiratory viral infections could lead to development of asthma, we still lack a mechanistic understanding on the virus-pathogen interactions that lead to durable cell reprograming and chronic disease. My future research will expand on this foundation to understand how multiple innate and adaptive immune cells initially engage respiratory viruses, and how infected cells can evade antiviral cytotoxicity to survive. I’m also interested in covering the mechanisms by which infected and survivor cells affect antiviral responses, viral adaptation, and the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD).

Speaker: Italo de Araujo Castro, Washington University