Human metapneumovirus (hMPV) is a leading cause of respiratory disease in children and the elderly. Initially identified in 2001 in samples collected from children with respiratory tract infection in the Netherlands, the clinical features of hMPV are similar to those of respiratory syncytial virus (RSV) and include mid-to-upper respiratory tract infection that may require hospitalization. The hMPV F protein is a trimeric class I viral fusion protein that has high conservation between viral subgroups (A1, A2, B1, and B2). hMPV can infect respiratory epithelial cells in the absence of the hMPV G protein, although hMPV G is required for viral fitness in vivo. The hMPV F protein contains an RGD motif, and the receptor has been hypothesized to be α5β1 integrin. Heparan sulfate has also been shown to have a role in hMPV F protein-mediated attachment.