Relatively recently discovered, human metapneumovirus (HMPV) is a human pathogen with worldwide prevalence, accounting for a substantial percentage of respiratory tract diseases. Concurrent viral and bacterial infections enable intricate mechanisms of cooperation between pathogens, which complicate the symptoms and outcome of the disease. Such bilateral interactions are based on the modulation of bacterial growth on epithelium pathologically altered during viral illness and the modulation of immune responses, as well as the enhancement of virus replication by bacterial virulence factors. This study showed that proteases produced by Porphyromonas gingivalis, a Gram-negative bacterium implicated in the development of periodontitis, named gingipains, facilitated HMPV replication in LLC-MK2 cells and may contribute to HMPV pathogenicity in patients with periodontitis. Gingipains at low nanomolar concentrations enabled HMPV replication and allowed virus propagation in vitro. In contrast to previously published data for influenza virus, however, Staphylococcus aureus proteases and human neutrophil elastase did not affect virus replication.