Effect of sialidase fusion protein (DAS 181) on human metapneumovirus infection of Hep-2 cells

Human metapneumovirus is an emerging cause of lower respiratory disease in infants, young children, and immunocompromised adults. We have previously demonstrated that human metapneumovirus infection is mediated by interaction of human metapneumovirus attachment (G) and/or fusion (F) proteins with cellular glycosaminoglycans. We report here the activity of an investigational sialidase fusion protein, DAS181, on human metapneumovirus infection of Hep-2 cells. These results suggest that human metapneumovirus infection may involve sialic acids, providing a new therapeutic strategy for human metapneumovirus for which there is currently no available treatment. Methods: Hep-2 cells were preincubated with DAS181 or control DAS185 (a mutated sialidase) prior to inoculation with human metapneumovirus strains. Infectivity was assessed by a cell-based ELISA quantitating human metapneumovirus matrix protein. The effect of DAS181 on binding of recombinant G attachment protein was also determined. Results: DAS181 blocked infection of human metapneumovirus strains A2, B1, and B2 at low concentrations. No effect of DAS185 was observed. Binding of MPV G protein to Hep-2 cells was also markedly inhibited by preincubation of cells with DAS181. Conclusions: These results suggest that human metapneumovirus may utilize sialic acids as an entry cofactor. DAS181 may thus represent a new therapeutic agent useful for the treatment of human metapneumovirus.