{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:36Z","timestamp":1787022216512,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014110","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32402854"],"award-info":[{"award-number":["32402854"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32272970"],"award-info":[{"award-number":["32272970"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2023YFE0106100"],"award-info":[{"award-number":["2023YFE0106100"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2022YFD1800301"],"award-info":[{"award-number":["2022YFD1800301"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Many RNA viruses exhibit error-prone replication. Continuous generation of erroneous copies accelerates evolution. Avian leukosis virus subgroup J (ALV-J), an avian oncogenic virus, is a classical model virus for studying retroviruses. ALV-J's high mutation rates drive continuous evolution of its envelope and pathogenicity, posing significant challenges to the poultry industry. Here we employed deep mutational scanning to systematically assess envelope-wide mutation effects on ALV-J replication, integrating high-throughput sequencing with mutant libraries to identify critical envelope residues impacting viral fitness. Following 10 passages, the library virus exhibited enhanced replication capacity. Moreover, the library virus derived from SPF chickens displays screening results similar to those of the DF-1 cell-passaged virus. Most mutations were progressively eliminated during viral passaging, especially the first 80 amino acids of ALV-J envelope. Critical amino acid mutations, preferential deletion\/insertion mutations and glycosylation patterns recapitulate evolutionary patterns observed in natural ALV-J isolates. Incorporation of all identified mutations into ALV-J J1 significantly increased in\n                    <jats:italic>vivo<\/jats:italic>\n                    replication efficiency and viral shedding of the recombinant virus. Functional study demonstrated that two key mutations independently promote viral replication: A64T enhancing entry via receptor-binding optimization, H304R promoting maturation through envelope cleavage efficiency. These insights enable targeted antiviral design by predicting evolutionary paths.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014110","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:34:25Z","timestamp":1774978465000},"page":"e1014110","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mapping the mutational landscape of an avian retrovirus envelope protein across its evolutionary trajectory"],"prefix":"10.1371","volume":"22","author":[{"given":"Moru","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5779-273X","authenticated-orcid":true,"given":"Aijian","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"issue":"7","key":"ppat.1014110.ref001","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.chom.2022.06.008","article-title":"The logic of virus evolution","volume":"30","author":"EV Koonin","year":"2022","journal-title":"Cell Host Microbe"},{"issue":"7","key":"ppat.1014110.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001005","article-title":"Quasispecies theory and the behavior of RNA viruses","volume":"6","author":"AS Lauring","year":"2010","journal-title":"PLoS Pathog"},{"issue":"7485","key":"ppat.1014110.ref003","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nature12861","article-title":"Mutational and fitness landscapes of an RNA virus revealed through population sequencing","volume":"505","author":"A Acevedo","year":"2014","journal-title":"Nature"},{"issue":"7490","key":"ppat.1014110.ref004","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature13087","article-title":"A predictive fitness model for influenza","volume":"507","author":"M Luksza","year":"2014","journal-title":"Nature"},{"issue":"6191","key":"ppat.1014110.ref005","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.1250939","article-title":"Microbial evolution. Global epistasis makes adaptation predictable despite sequence-level stochasticity","volume":"344","author":"S Kryazhimskiy","year":"2014","journal-title":"Science"},{"key":"ppat.1014110.ref006","first-page":"587","article-title":"Leukosis\/Sarcoma Group.","volume-title":"Diseases of Poultry. Leukosis\/Sarcoma Group 1","author":"V. 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