Analysis of Viral Genes and Host Responses Influencing the Severity of Influenza Virus and Respiratory Syncytial Virus Infection Viral proteins and host cell responses are key determinants of the severity of viral infections of the respiratory tract. To identify viral genes and mutations that influence the severity of influenza virus and respiratory syncytial virus (RSV) infections, we are isolating and sequencing these viruses from subjects experiencing mild or severe disease. In addition, we have access to a unique repository of human respiratory samples collected over 30 years from patients with different disease severities and clinical histories. We will use deep sequencing of expressed viral and host genes to identify viral mutations that correlate with disease severity and host cellular pathways triggered by infection. This research will guide the development of new antivirals and vaccination strategies. Immunofluorescence images of tissue culture cells infected with a clinical isolate of influenza virus. Viral nucleoprotein (green) was analyzed by indirect immunofluorescence using a mouse anti-nucleoprotein monoclonal antibody, followed by FITC-labeled goat anti-mouse antibody; cell nuclei (blue) were stained with DAPI.