{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:18:35Z","timestamp":1787980715573,"version":"build-2784847793"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 AI140442"],"award-info":[{"award-number":["R01 AI140442"]}]},{"name":"NIH","award":["R01 AI169537"],"award-info":[{"award-number":["R01 AI169537"]}]},{"name":"NIH","award":["DC022549"],"award-info":[{"award-number":["DC022549"]}]},{"award":["R01 AI140442"],"award-info":[{"award-number":["R01 AI140442"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI169537"],"award-info":[{"award-number":["R01 AI169537"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DC022549"],"award-info":[{"award-number":["DC022549"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Pennsylvania Institute for Infectious and Zoonotic Diseases"},{"name":"Brody Family Medical Trust Fund Fellowship in \u201cIncurable Diseases\u201d of The Philadelphia Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Clade A Middle East respiratory syndrome coronavirus (MERS-CoV) spilled over from camels into humans in Saudi Arabia in 2012 and caused pneumonia and severe respiratory disease, with a 37% case fatality rate. While clade A and B viruses are closely related phylogenetically, clade B MERS-CoV strains have since outcompeted clade A strains and continue to circulate in camels and humans in the Middle East and cause outbreaks in humans. Clade C strains circulate in camels across the African continent but have not been reported to cause disease in humans. We have shown that a number of East African clade C isolates are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures, which may underlie the reduced replication of East African clade C strains in humans. However, the reduced replicative capacity of West African strains in human cells appears to be independent of viral entry, suggesting an alternative basis for their attenuation. Here, we report that West African clade C MERS-CoV isolates with deletions in ORF4b encoding a key accessory protein, NS4b, induced significantly more robust interferon and inflammatory responses than clade A MERS in human respiratory cell lines and primary bronchial air\u2013liquid interface cultures. The replication deficit for the West African strain BF785, which has a complete deletion of ORF4b, was partially rescued when RNASEL was knocked out in A549 cells. These findings demonstrate that complete loss of NS4b results in stronger innate immune activation than partial truncation and suggests that differential selection on NS4b may contribute to the varying phenotypes of clade C MERS-CoV strains circulating in African camels.<\/jats:p>","DOI":"10.3390\/v18090935","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:21Z","timestamp":1787828301000},"page":"935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["West African Clade C MERS-CoV Strains BF785 and Mor213 Induce More Robust Interferon and Inflammatory Signaling Compared to Clade A in Human Respiratory Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-3473","authenticated-orcid":false,"given":"Helen A.","family":"Stillwell","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Penn Center for Research on Emerging Viruses, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Winstone","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Penn Center for Research on Emerging Viruses, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-7758","authenticated-orcid":false,"given":"Cailu","family":"Lin","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7591-4946","authenticated-orcid":false,"given":"Anant K.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Penn Center for Research on Emerging Viruses, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Hui","family":"Tan","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-7082","authenticated-orcid":false,"given":"Sunil","family":"Singhal","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-6107","authenticated-orcid":false,"given":"Danielle R.","family":"Reed","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, PA 19104, USA"},{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA"},{"name":"Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-4528","authenticated-orcid":false,"given":"Susan R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Penn Center for Research on Emerging Viruses, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-1535","authenticated-orcid":false,"given":"Ranawaka A. P. M.","family":"Perera","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Penn Center for Research on Emerging Viruses, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2213-2600(26)00049-4","article-title":"Respiratory infections due to human common cold coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2: Epidemiology, pathogenesis, clinical features, diagnostics, therapeutics, and vaccine landscapes","volume":"14","author":"Zumla","year":"2026","journal-title":"Lancet Respir. 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