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Within the alphacoronaviruses is the species\n                      <jats:italic toggle=\"yes\">Alphacoronavirus-1<\/jats:italic>\n                      , which comprises distinct viruses of cats, dogs, and pigs, along with a separate species that infects mustelids\u2014as well as other related viruses of pigs and circulating human viruses. High-pathogenicity feline coronavirus (FCoV) is infamous as the cause of feline infectious peritonitis (FIP), existing as two distinct genotypes (types 1 and 2) and transmitted as a low-pathogenicity virus. The high-pathogenicity variants arise in cats infected with FCoV, and while the mutations responsible remain enigmatic, the main determinant is the spike glycoprotein. FCoV-1 disease outcome is driven by a combination of both within- and between-host evolution. Virulence can be largely explained by the \u201cinternal mutation hypothesis,\u201d which argues that high-pathogenicity\u2014but poorly transmissible\u2014variants are selected in individual cats. Canine coronaviruses are generally considered low pathogenicity but can cause severe enteritis and can be systemic. Notably, the canine coronavirus spike gene periodically recombines with FCoV-1 to generate FCoV-2, exemplified by FCoV-23, which has caused a widespread outbreak of FIP in Cyprus and has a notably truncated spike N-terminal domain (NTD). In pigs, coronaviruses often cause severe gastrointestinal disease but can become respiratory and have low pathogenicity based on what can also be considered an \u201cinternal deletion\u201d of the spike NTD. These viruses may exist as a dynamic \u201cmetavirome\u201d (the sum of all viral genomes present in a sample) that is in a constant state of flux, presenting notable challenges for disease surveillance and management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01921-25","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T13:00:19Z","timestamp":1756386019000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Rethinking the drivers of coronavirus virulence and pathogenesis; toward an understanding of the dynamic world of mutations, indels, and recombination within the alphacoronaviruses"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-9622","authenticated-orcid":false,"given":"Ximena A.","family":"Olarte-Castillo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Microbiology & Immunology and Public & Ecosystem Health, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Frazier","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Microbiology & Immunology and Public & Ecosystem Health, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Gomes Noll","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Microbiology & Immunology and Public & Ecosystem Health, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Choi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Microbiology & Immunology and Public & Ecosystem Health, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-3816","authenticated-orcid":true,"given":"Gary R.","family":"Whittaker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Microbiology & Immunology and Public & Ecosystem Health, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202871119"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12010083"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/v4061011"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2023.199059"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/vetr.3143"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09340-0"},{"key":"e_1_3_2_8_2","first-page":"23","article-title":"Widespread outbreak of FIP in Cyprus with a suspected highly virulent feline coronavirus strain","volume":"53","author":"Hardas A","year":"2023","unstructured":"Hardas A, Attipa C, Gunn-Moore D, Epaminondas D, Lyraki M, Gentil M, Loukaidou S, Mazeri S. 2023. 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