{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:37:31Z","timestamp":1789144651478,"version":"build-2803163510"},"reference-count":142,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":73,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Biomedical and Bioengineering","award":["T32EB023860"],"award-info":[{"award-number":["T32EB023860"]}]},{"name":"NIH\/NIAID","award":["R01 AI134384"],"award-info":[{"award-number":["R01 AI134384"]}]},{"name":"FDA Vet-LIRN","award":["1U18FD006993-01"],"award-info":[{"award-number":["1U18FD006993-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Feline coronaviruses (FCoVs) commonly cause mild enteric infections in felines worldwide (termed feline enteric coronavirus [FECV]), with around 12 per cent\u2009developing into deadly feline infectious peritonitis (FIP; feline infectious peritonitis virus [FIPV]). Genomic differences between FECV and FIPV have been reported, yet the putative genotypic basis of the highly pathogenic phenotype remains unclear. Here, we used state-of-the-art molecular evolutionary genetic statistical techniques to identify and compare differences in natural selection pressure between FECV and FIPV sequences, as well as to identify FIPV- and FECV-specific signals of positive selection. We analyzed full-length FCoV protein coding genes thought to contain mutations associated with FIPV (Spike, ORF3abc, and ORF7ab). We identified two sites exhibiting differences in natural selection pressure between FECV and FIPV: one within the S1\/S2 furin cleavage site (FCS) and the other within the fusion domain of Spike. We also found fifteen sites subject to positive selection associated with FIPV within Spike, eleven of which have not previously been suggested as possibly relevant to FIP development. These sites fall within Spike protein subdomains that participate in host cell receptor interaction, immune evasion, tropism shifts, host cellular entry, and viral escape. There were fourteen sites (twelve novel sites) within Spike under positive selection associated with the FECV phenotype, almost exclusively within the S1\/S2 FCS and adjacent to C domain, along with a signal of relaxed selection in FIPV relative to FECV, suggesting that furin cleavage functionality may not be needed for FIPV. Positive selection inferred in ORF7b was associated with the FECV phenotype and included twenty-four positively selected sites, while ORF7b had signals of relaxed selection in FIPV. We found evidence of positive selection in ORF3c in FCoV-wide analyses, but no specific association with the FIPV or FECV phenotype. We hypothesize that some combination of mutations in FECV may contribute to FIP development, and that it is unlikely to be one singular \u2018switch\u2019 mutational event. This work expands our understanding of the complexities of FIP development and provides insights into how evolutionary forces may alter pathogenesis in coronavirus genomes.<\/jats:p>","DOI":"10.1093\/ve\/vead019","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T09:29:34Z","timestamp":1678872574000},"source":"Crossref","is-referenced-by-count":26,"title":["Natural selection differences detected in key protein domains between non-pathogenic and pathogenic feline coronavirus phenotypes"],"prefix":"10.1093","volume":"9","author":[{"given":"Jordan D","family":"Zehr","sequence":"first","affiliation":[{"name":"Department of Biology, Temple University, Institute for Genomics and Evolutionary Medicine , Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei L","family":"Kosakovsky Pond","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Institute for Genomics and Evolutionary Medicine , Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-3688","authenticated-orcid":false,"given":"Jean K","family":"Millet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, INRAE, UVSQ, Virologie et Immunologie Mol\u00e9culaires , Jouy-en-Josas 78352, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-9622","authenticated-orcid":false,"given":"Ximena A","family":"Olarte-Castillo","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"},{"name":"James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-6088","authenticated-orcid":false,"given":"Alexander G","family":"Lucaci","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Institute for Genomics and Evolutionary Medicine , Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-9953","authenticated-orcid":false,"given":"Stephen D","family":"Shank","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Institute for Genomics and Evolutionary Medicine , Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6682-0031","authenticated-orcid":false,"given":"Kristina M","family":"Ceres","sequence":"additional","affiliation":[{"name":"Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"},{"name":"Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-3816","authenticated-orcid":false,"given":"Gary R","family":"Whittaker","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"},{"name":"Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-3092","authenticated-orcid":false,"given":"Laura B","family":"Goodman","sequence":"additional","affiliation":[{"name":"James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"},{"name":"Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Stanhope","sequence":"additional","affiliation":[{"name":"Department of Public and Ecosystem Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"2023040811593320700_","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1099\/vir.0.19129-0","article-title":"Persistence and Transmission of Natural Type I Feline Coronavirus Infection","volume":"84","author":"Addie","year":"2003","journal-title":"The Journal of General Virology"},{"key":"2023040811593320700_","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.jfms.2009.05.008","article-title":"Feline Infectious Peritonitis. ABCD Guidelines on Prevention and Management","volume":"11","author":"Addie","year":"2009","journal-title":"Journal of Feline Medicine and Surgery"},{"key":"2023040811593320700_","doi-asserted-by":"crossref","DOI":"10.1177\/2055116919856103","article-title":"Distinct Mutation in the Feline Coronavirus Spike Protein Cleavage Activation Site in a Cat with Feline Infectious Peritonitis-associated Meningoencephalomyelitis","volume":"5","author":"Andr\u00e9","year":"2019","journal-title":"Journal of Feline Medicine and Surgery Open Reports"},{"key":"2023040811593320700_","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.vetmic.2014.07.020","article-title":"Mutations of 3c and Spike Protein Genes Correlate with the Occurrence of Feline Infectious Peritonitis","volume":"173","author":"Bank-Wolf","year":"2014","journal-title":"Veterinary 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