Kamio Noriaki, Cueno Marni E, Takagi Asako, Imai Kenichi
Department of Microbiology and Immunology, Nihon University School of Dentistry, Tokyo, Japan.
Department of Microbiology and Immunology, Nihon University School of Dentistry, Tokyo, Japan.
J Biol Chem. 2025 Feb;301(2):108166. doi: 10.1016/j.jbc.2025.108166. Epub 2025 Jan 8.
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.
流感是一个全球性的健康问题，在老年人中会导致严重的发病和死亡；因此，其预防至关重要。在流感病毒感染期间，血凝素（HA）的裂解对于病毒进入宿主细胞至关重要。流感病毒与细菌的相互作用会影响感染的致病性，特定细菌通过参与HA裂解来加重疾病的严重程度。口腔卫生差和口腔细菌的存在与流感有关。牙龈卟啉单胞菌是一种牙周病原菌，尤其与流感相关；然而，其潜在机制仍不清楚。在本研究中，我们观察到牙龈卟啉单胞菌培养上清液促进了病毒释放和感染的细胞间传播。进一步研究发现，该上清液中含有裂解的HA。因此，我们聚焦于牙龈蛋白酶（Rgp和Kgp），它们是牙龈卟啉单胞菌产生的类胰蛋白酶。我们确定Rgp抑制剂可抑制HA裂解以及与牙龈卟啉单胞菌培养上清液相关的病毒释放增加，而Kgp抑制剂未观察到此类效果。此外，缺乏Rgp的牙龈卟啉单胞菌培养上清液无法裂解HA、增强病毒传播或增加病毒释放。相反，缺乏Kgp的牙龈卟啉单胞菌培养上清液可裂解HA并促进感染。这些结果表明，牙龈卟啉单胞菌分泌的Rgp有可能通过裂解HA来激活流感病毒的感染性，这表明了解牙龈卟啉单胞菌对流感病毒感染的影响将有助于制定流感预防措施。
