{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:23:45Z","timestamp":1781108625980,"version":"3.54.1"},"reference-count":75,"publisher":"National Academy of Sciences","issue":"18","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE031756"],"award-info":[{"award-number":["DE031756"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:p>\n                    Physical interactions with bacterial colonizers at mucosal barrier surfaces can have beneficial or detrimental effects on viral infectivity and transmission. The oropharyngeal mucosal surface is a major portal of entry for many pathogenic respiratory viruses, such as respiratory syncytial virus (RSV), and also harbors a rich and diverse microbiome. Whether oropharyngeal bacteria directly or indirectly influence host susceptibility to respiratory viruses remains unknown. Here, we show that\n                    <jats:italic toggle=\"yes\">Porphyromonas gingivalis<\/jats:italic>\n                    , an oral pathobiont, potently and uniquely suppresses airway epithelial antiviral immunity by degrading interferons (IFNs) and transcriptionally repressing multiple IFN-stimulated genes (ISGs), which are essential for providing resistance to viral infection. Despite inducing a state of IFN hyporesponsiveness, we found that\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    counterintuitively protected against severe infection by RSV and the closely related murine-specific Sendai virus (SeV) in two independent models: human airway bronchial epithelial transwell cultures and airway infection in mice. This protection was conferred by the activity of\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    cysteine proteases (gingipains) that cleaved envelope glycoproteins on RSV and SeV, thereby impairing their infectious capacity. Thus, our data show a nuanced role for\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    in modulating host susceptibility to viral infection. While\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    can significantly inhibit host IFN responses, its proteases preemptively reduce viral infectious capacity, protecting the host from severe damage associated with respiratory infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2503100123","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:03:43Z","timestamp":1777572223000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Gingipain proteases from the bacterium\n                    <i>Porphyromonas gingivalis<\/i>\n                    confer protection against airway viral infection"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9000-6427","authenticated-orcid":false,"given":"Carlos J.","family":"Rodriguez Hernandez","sequence":"first","affiliation":[{"name":"Center for Microbe 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University","place":["Louisville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville","place":["Louisville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6415-1192","authenticated-orcid":false,"given":"Katherine","family":"Carey","sequence":"additional","affiliation":[{"name":"Center for Microbe and Immunity Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital","place":["Columbus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8354-8811","authenticated-orcid":false,"given":"Michelle","family":"Rohlfing","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s 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Children\u2019s Hospital","place":["Columbus"]},{"name":"Division of Allergy and Immunology, Department of Pediatrics, Nationwide Children\u2019s Hospital and The Ohio State University College of Medicine","place":["Columbus"]},{"name":"Department of Pediatrics, The Ohio State University College of Medicine","place":["Columbus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville","place":["Louisville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Artyomov","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3147-5039","authenticated-orcid":false,"given":"Richard 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Potempa, K. A. Nguyen, Purification and characterization of gingipains. Curr. Protoc. Protein Sci. Chapter 21, 21.20.1\u201321.20.27 (2007).","journal-title":"Curr. Protoc. Protein Sci."},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm.1997.378.3-4.223"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00986-09"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3535"},{"key":"e_1_3_4_72_2","unstructured":"C. J. Rodriguez-Hernandez Porphyromonas gingivalis inhibits Respiratory Syncytial Virus infection while suppressing anti-viral immunity. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE281938. Deposited 14 November 2024."},{"key":"e_1_3_4_73_2","unstructured":"K. Leskinen Expression profiling by high throughput sequencing. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE182847. Deposited 26 August 2021."},{"key":"e_1_3_4_74_2","unstructured":"S. P. Jochems Expression profiling by high throughput sequencing. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE124949. Deposited 11 January 2019."},{"key":"e_1_3_4_75_2","unstructured":"R. Aprianto J. Slager S. Holsappel J. Veening Expression profiling by high throughput sequencing. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE79595. 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