{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:27:27Z","timestamp":1789036047422,"version":"build-2803163510"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI153602,R21-AI145400"],"award-info":[{"award-number":["R01-AI153602,R21-AI145400"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["Investigators in the Pathogenesis of Infectious Disease"],"award-info":[{"award-number":["Investigators in the Pathogenesis of Infectious Disease"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute of Human Infections and Immunity University of Texas Medical Branch","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100007130","name":"University of Texas System","doi-asserted-by":"publisher","award":["STARs Award"],"award-info":[{"award-number":["STARs Award"]}],"id":[{"id":"10.13039\/100007130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>During the early stages of the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOCs) independently acquired mutations in the highly variable 203\u2013205 amino acid region of the nucleocapsid (N) protein including R203K + G204R (found in the Alpha, Gamma, and Omicron variants), R203M (in Delta), and T205I (in Beta). In previous research, we demonstrated that the R203K + G204R mutation significantly enhances SARS-CoV-2 N phosphorylation, which subsequently increases viral fitness and pathogenesis. In this study, we investigated the effects of the R203M and T205I mutations on SARS-CoV-2 infection. Using reverse genetics, we introduced these mutations into the early pandemic Washington-1 (WA-1) strain and observed that both the R203M and T205I mutants enhanced replication and viral fitness. However, unlike the R203K + G204R mutant, the R203M and T205I mutants caused only moderate changes in lung pathology. Notably, each mutation\u2014R203K + G204R, R203M, and T205I\u2014induced distinct patterns of N phosphorylation, which likely contribute to the observed phenotypic differences between the mutants. Interestingly, when bat cells expressing human ACE2 were infected with these mutants, we observed a reduction, rather than an enhancement, in both SARS-CoV-2 replication and N phosphorylation. Collectively, our findings suggest that the R203K + G204R, R203M, and T205I mutations are a result of convergent evolution and reflect how SARS-CoV-2 has adapted for human infection.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>After its emergence, SARS-CoV-2 rapidly adapted to human infection, acquiring numerous mutations across its genome. Many of these mutations remain uncharacterized. This study examines a mutational hotspot among SARS-CoV-2 variants: residues 203\u2013205 of the nucleocapsid (N) protein. We demonstrate that three unique mutations identified in this region among variants of concern enhance infection in human cells and animal models while eliciting distinct patterns of N protein phosphorylation. Intriguingly, these same mutations reduce both N protein phosphorylation and viral replication in bat cells. These findings suggest that each mutation represents independent adaptation by variants of concern for human infection. Importantly, this study underscores the critical role of these mutations in facilitating the expansion of SARS-CoV-2 into human populations and highlights the potential for similar mutations to drive future zoonotic coronavirus outbreaks.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.02091-24","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:02:22Z","timestamp":1749718942000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Convergent evolution in nucleocapsid facilitated SARS-CoV-2 adaptation for human infection"],"prefix":"10.1128","volume":"99","author":[{"given":"Kumari G.","family":"Lokugamage","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]},{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Elias","family":"Alvarado","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Plante","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"World Reference Center of Emerging Viruses and Arboviruses, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Ahearn","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Estes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Meyers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Nilsson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035b05819","id-type":"ROR","asserted-by":"publisher"}],"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-5990","authenticated-orcid":true,"given":"Andrew L.","family":"Routh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch","place":["Galveston, USA"]},{"name":"Department of Immunology and Microbiology, Scripps Research","place":["La Jolla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Walker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch","place":["Galveston, USA"]},{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-7606","authenticated-orcid":true,"given":"Vineet D.","family":"Menachery","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]},{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics & Emory Vaccine Center, Emory University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-1255","authenticated-orcid":true,"given":"Bryan A.","family":"Johnson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, The University of Texas Medical Branch","place":["Galveston, USA"]},{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Human Infection and Immunity, The University of Texas Medical Branch","place":["Galveston, USA"]},{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Tropical Diseases, The University of Texas Medical Branch","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"Wolrd Health Organization. 2023. 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