Porphyromonas gingivalis inhibits Respiratory Syncytial Virus infection while suppressing anti-viral immunity

Colonizing microbiota can differentially impact the outcomes of viral infections. While synergistic interactions between invading viruses and specific bacterial colonizers can enhance viral infectivity, resulting in severe disease, other bacteria can play a more antagonistic role by destabilizing viral particles, thus protecting against infection. Here, we explored whether Porphyromonas gingivalis (Pg), a periodontal bacterial pathogen that can translocate to the airways, increases susceptibility to infection with the respiratory syncytial virus (RSV) and Sendai virus (SeV). Using a model of primary human bronchial epithelial (HBE) air-liquid interface cultures, we found that Pg co-infection significantly reduced RSV infection by rapidly inactivating RSV particles. This protection was conferred by the proteolysis of RSV fusion and attachment proteins by Pg proteases (gingipains), thus limiting viral entry. Despite this initial bottleneck, RSV replication within Pg co-infected cells was higher, indicating Pg created an intracellular environment favorable for viral replication. RNA-seq studies revealed that Pg infection led to the broad suppression of interferons (IFNs), particularly IFN-λ, and downstream interferon-stimulated genes (ISGs). Thus, our data show that P. gingivalis initially restricts RSV infection by inactivating the virus but later facilitates viral replication by suppressing IFNs. Our findings are clinically relevant as RSV infections are significant health concerns in both pediatric populations and older adults, who have a higher prevalence of periodontitis.