Grant: Operating Grant

Human metapneumovirus is a newly-described respiratory virus that has been associated with bronchiolitis, pneumonia and asthma exacerbations especially in young children. It is an important pathogen that has been consistently reported as the second or third cause of hospitalization for respiratory tract infections in children less than 3 years of age. In the next 5 years, we plan to study in more details the pathogenesis (mechanism of disease) of this new viral pathogen in cell culture systems and in a relevant mouse model of pneumonia by focusing mainly on the role of the fusion protein in viral entry into the cells. In particular, we seek to determine whether more fusogenic viruses producing syncytia (large mutinucleated cells) obtained from patients' samples or generated in the laboratory will be more virulent and thus will result in increased mortality in mice. We finally propose to develop and evaluate new antiviral agents (mainly fusion inhibitors) and vaccine candidates (intra muscular and intra-nasal subunit and live-attenuated vaccines) in two animal models (mice and cotton rats). These studies are particularly relevant since there are no approved therapeutic or prophylactic modalities against such viral infection at the present time. At term, our work should lead to a better understanding of human metapneumovirus mutations associated with severe infections and to the development of innovative strategies to treat or prevent respiratory diseases caused by this important pediatric pathogen.