Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281938 | GEO | 2026/04/17

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and older adults. Several vaccines have recently been approved, which are all based on the RSV fusion (F) protein. Among the strategies to induce a broader immune response is the development of live-attenuated RSV vaccines, for example by disabling nonstructural protein 1 (NS1). RSV NS1 has been found to modulate the host immune response by repression of interferon (IFN) production. However, functional characterization of this protein was mainly performed in immortalized cell lines, which do not necessarily represent the in vivo situation. Here, we assessed the effect of NS1 mutations on replication and host responses in differentiated primary human nasal epithelial cells (HNEC) cultured at air-liquid interface (ALI), which mimic several physiological properties of the human airways. Using a newly developed yeast-based RSV reverse genetics system, inactivating mutations in the NS1 gene were introduced. These mutations did not affect viral replication in Vero and A549 cells. However, in HNEC we observed a delayed replication of the NS1 mutants compared to the WT virus. Bulk RNA sequencing data from early post infection revealed a stronger antiviral signature in HNEC that were infected with NS1 mutants compared to WT, characterized by upregulation of IFN-β and IFN-λ1/2/3 and chemokines CXCL11 and CCL5. This signature was confirmed by analysis of the cytokines that were released into the HNEC basal medium. Finally, the basal medium containing these cytokines was used for an indirect immune cell migration assay. In this set-up, both WT and NS1 mutant viruses induce migration of mainly neutrophils. In conclusion, this study shows that RSV NS1 supports viral replication not only via inhibition of the production of IFNs, but also by reducing early chemokine production and secretion by epithelial cells. Furthermore, our data highlight the suitability of the ALI transwell model for preclinical assessment of live-attenuated vaccine candidates.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets