Variability in Fusogenic Activity of Human Metapneumovirus Fusion Protein from Different Strains

Abstract

First identified in 2001, the paramyxovirus human metapneumovirus (HMPV) is a novel pathogen that causes viral respiratory disease in infants, the elderly, and immunocompromised patients worldwide and is the second most common cause of pediatric lower respiratory illness, following the closely related RSV. Despite its clinical significance, little is known about its entry pathway, complicating the search for antivirals. Of the three surface glycoproteins expressed on the viral membrane, the attachment protein, a small hydrophobic protein, and the fusion protein F, only the F protein is required for membrane fusion and infectivity. The F protein undergoes a dramatic conformational change in order to bring the viral and target cell membranes together. This conformation change in HMPV strain CAN97–83 has been shown to be triggered by low pH. However, low pH triggering varies between F proteins of different strains. In this study we characterized fusogenic activity of strains representative of all four clades using two independent fusion assays, syncytia formation and luciferase reporter gene assay. Our results suggest that both the overall fusion level and the amount of stimulation by low pH vary between F proteins of different strains. Comparison of F protein sequence will be used to identify potential critical residues. This research was supported by NIH grant R01AI051517.