Project Director: Tanya Miura

Project Team: Craig Miller, Onesmo Balemba, Jake Ferguson, Jagdish Patel, JT Van Leuven, Andres Gonzalez

Viral infections in the lower respiratory tract cause severe disease and are responsible for a majority of pediatric hospitalizations, approximately 20% of which are infected by more than one viral pathogen. Clinical data indicate that disease severity can be enhanced, reduced or be unaffected by viral co-infection. However, it is not clear how unrelated viruses interact within the context of a complex host to determine disease severity. The long-term goal of this research is to uncover the causal relationships between co-infection and the resulting respiratory disease severity. Variables that will potentially predict disease severity include viral strains, doses, timing, viral competition, genetic variation in the host, and the immune response. The proposed research will develop a murine model with cellular and organismal components and a human in vitro model to test the central hypothesis that respiratory viral co-infections change disease severity both by direct viral interactions and by modulating host responses. Statistical and stochastic modeling will reveal the complex interactions between heterologous viruses within their shared target cells and host organisms.