{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:19:15Z","timestamp":1779387555319,"version":"3.53.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014229","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MC133"],"award-info":[{"award-number":["ZR2022MC133"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010038","name":"Earmarked Fund for China Agriculture Research System","doi-asserted-by":"publisher","award":["CARS-41-Z17"],"award-info":[{"award-number":["CARS-41-Z17"]}],"id":[{"id":"10.13039\/501100010038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Avian leukosis virus (ALV), a prototypic alpharetrovirus, serves as a pivotal model for studying retroviral biology due to its well-characterized replication cycle, genetic tractability, and evolutionary conservation with clinically relevant retroviruses like HIV. This study identified 12 novel lysine acetylation (KAc) sites in ALV proteins through mass spectrometry, revealing striking conservation across multiple ALV subgroups and distributed as follows: 3 in the matrix (MA) protein, 1 in the capsid (CA) protein, 1 in the reverse transcriptase (RT) protein, and 7 clustered in the integrase (IN) protein. Functional characterization via site-directed mutagenesis demonstrated that the majority of these sites serve as critical regulatory switches during viral replication, with individual KAc modifications at distinct sites differentially regulating ALV replication. Mechanistically, we discovered that the host acetyltransferase HAT1 physically interacts with ALV RT protein to mediate its acetylation at the evolutionarily conserved RT13K residue. This modification, which is conserved across multiple ALV subgroups and other retroviral species, significantly enhances both RT enzymatic activity and viral replication efficiency. Our findings establish KAc as a critical post-translational regulator of alpharetrovirus replication and demonstrate that RT13K acetylation is a key modulator of ALV RT function. The conservation of this site across retrovirals suggests its functional importance and warrants further investigation to explore its potential as a broad-spectrum antiviral target. These results not only deepen understanding of epigenetic regulation in viral replication but also provide a framework for developing acetylation-targeted antiretroviral strategies.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014229","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:39:55Z","timestamp":1779125995000},"page":"e1014229","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acetylation-mediated regulation of ALV viral proteins: Implications for retroviral 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