Porphyromonas gingivalis gingipain potentially activates influenza A virus infectivity through proteolytic cleavage of viral hemagglutinin.

Influenza is a worldwide health problem that causes significant morbidity and mortality among the elderly; therefore, its prevention is important. During influenza virus infection, the cleavage of hemagglutinin (HA) is essential for the virus to enter host cells. Influenza virus-bacteria interactions influence the pathogenicity of infections, and specific bacteria contribute to the severity of the disease by participating in HA cleavage. Poor oral hygiene and the presence of oral bacteria are associated with influenza. Porphyromonas gingivalis, a periodontopathic bacterium, is particularly associated with influenza; however, the underlying mechanisms remain unclear. In the present study, we observed P. gingivalis culture supernatant promoted viral release and cell-to-cell spread of the infection. Further investigation revealed that the supernatant contained cleaved HA. Therefore, we focused on gingipains (Rgp and Kgp) which are trypsin-like proteases produced by P. gingivalis. We determined that the Rgp inhibitor inhibited both HA cleavage and the increase in virus release associated with the P. gingivalis culture supernatant, whereas such effects were not observed with the Kgp inhibitor. In addition, Rgp-deficient P. gingivalis culture supernatant failed to cleave HA, enhance virus spread, or increase virus release. In contrast, Kgp-deficient P. gingivalis culture supernatant cleaved HA and promoted infection. These results indicated that P. gingivalis-secreted Rgp has the potential to activate influenza virus infectivity through HA cleavage, suggesting that understanding the effects of P. gingivalis on influenza virus infection will contribute to the establishment of influenza prevention measures.