Breaking in: human metapneumovirus fusion and entry

Abstract

This project is concerned with how the recently discovered paramyxovirus, human metapneumovirus (HMPV), interacts with host cells to initiate entry. In this dissertation I explore whether the HMPV fusion protein interacts with cellular proteins during virus attachment and whether receptor binding is sufficient to initiate virus-mediated fusion at the cell surface. In this research I developed novel techniques to study HMPV fusion and entry. I learned that the HMPV fusion protein uses RGD-binding integrins to mediate attachment and virus entry, binding to integrins is not sufficient to trigger HMPV fusion, and HMPV fuses with intracellular membranes instead of at the cell surface. In sum, I have elucidated mechanisms that HMPV utilizes to mediate virus entry, which are unique from the entry mechanism used by other paramyxoviruses.