{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T05:07:59Z","timestamp":1767503279676,"version":"3.48.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":216,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"One Health Research Seed"},{"DOI":"10.13039\/100020477","name":"Edward Via College of Osteopathic Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020477","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects humans and animals and is therefore a pathogen of grave concern within a One Health framework. Identifying animal-adaptive mutations is critical to preserving One Health, as these mutations could also lead to the persistence of SARS-CoV-2 in animal reservoirs with continual spillover to humans. Therefore, we sought to pair experimental evolution and epidemiological data to identify putative human- and animal-adaptive viral residues and determine their impact on replication-competent SARS-CoV-2 in both human and animal cells. We passaged SARS-CoV-2 in cells expressing human, dog, cat, mink, and white-tailed deer ACE2 and sequenced the passaged populations. In addition, we searched SARS-CoV-2 sequences for mutations following patterns of convergent evolution that were common to both human- and animal-derived SARS-CoV-2 sequences. We identified the epidemiologically relevant Spike A222V mutation from our passaging experiment in cells expressing cat ACE2, a mutation that has also arisen independently across eight lineages of SARS-CoV-2 from human- and animal-derived sequences. To assess its impact on replication in human and animal cells, we constructed SARS-CoV-2 Spike A222V in the Wuhan-Hu-1 backbone with Spike D614G; this virus replicated similarly to the WT SARS-CoV-2 in human lung epithelial cells. In contrast, SARS-CoV-2 Spike A222V demonstrated an advantage in replication in primary deer lung cells, which was not mediated by the deer ACE2 receptor. Infection via the human, dog, cat, and mink ACE2 receptor resulted in reduced replication of SARS-CoV-2 Spike A222V. Our experiments identified Spike A222V as a putatively deer-adaptive mutation. Future studies should assess Spike A222V\u2019s relevance to transmission within deer and to other animal species in contact with deer.<\/jats:p>","DOI":"10.1093\/ve\/veaf059","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T11:20:54Z","timestamp":1754306454000},"source":"Crossref","is-referenced-by-count":1,"title":["The recurrent Spike A222V mutation in SARS-CoV-2 enhances replication in primary deer lung cells"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4710-5323","authenticated-orcid":false,"given":"Chelsea","family":"Cereghino","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, 205 Duck Pond Drive, VA-MD College of Veterinary Medicine at Virginia Tech , Blacksburg, VA 24061 ,","place":["United States"]},{"name":"Center for Emerging, Zoonotic, and Vector-borne Pathogens, Fralin Life Sciences Institute, Virginia Tech Corporate Research Center (CRC), Integrated Life Science Building (ILSB) 1981 Kraft Dr , Room 2036, Blacksburg, VA 24060 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kateland","family":"Tiller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, 205 Duck Pond Drive, VA-MD College of Veterinary Medicine at Virginia Tech , Blacksburg, VA 24061 ,","place":["United States"]},{"name":"Center for Emerging, Zoonotic, and Vector-borne Pathogens, Fralin Life Sciences Institute, Virginia Tech Corporate Research Center (CRC), Integrated Life Science Building (ILSB) 1981 Kraft Dr , Room 2036, Blacksburg, VA 24060 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Edward Via College of Osteopathic Medicine , 4408 Bon Aire Drive, Monroe, LA 71203 ,","place":["United States"]},{"name":"College of Pharmacy, University of Louisiana Monroe , 1800 Bienville Dr, Monroe, LA 71201 ,","place":["United States"]},{"name":"Center for One Health Research, VA-MD College of Veterinary Medicine , 1410 Prices Ford Road, Blacksburg, VA 24060 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel","family":"Michalak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Edward Via College of Osteopathic Medicine , 4408 Bon Aire Drive, Monroe, LA 71203 ,","place":["United States"]},{"name":"Center for One Health Research, VA-MD College of Veterinary Medicine , 1410 Prices Ford Road, Blacksburg, VA 24060 ,","place":["United States"]},{"name":"Institute of Evolution, University of Haifa , 199 Abba Khoushy Ave., Mount Carmel, Haifa, 3103301, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9483-1694","authenticated-orcid":false,"given":"James","family":"Weger-Lucarelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, 205 Duck Pond Drive, VA-MD College of Veterinary Medicine at Virginia Tech , Blacksburg, VA 24061 ,","place":["United States"]},{"name":"Center for Emerging, Zoonotic, and Vector-borne Pathogens, Fralin Life Sciences Institute, Virginia Tech Corporate Research Center (CRC), Integrated Life Science Building (ILSB) 1981 Kraft Dr , Room 2036, Blacksburg, VA 24060 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"2026010400065404400_ref1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9070529","article-title":"Evidence for SARS-CoV-2 infection of animal 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