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Notably, the utility of potato virus Y (PVY), the type member of the genus\n                    <jats:italic>Potyvirus<\/jats:italic>\n                    , is severely hampered by its elicitation of tobacco vein necrosis (TVN). Here, we demonstrate that a single synonymous substitution (AAA to AAG) at the K178 codon of P1 causes almost no TVN. Mechanistically, the P1\u2010AAG mutation attenuates the synergistic RNA silencing suppression (RSS) activity typically mediated by the P1\/HC\u2010Pro complex. This functional impairment abrogates the virus\u2010induced upregulation of specific host microRNAs (miR6020, miR6164 and miR6021). Using this non\u2010necrotic PVY\u2010P1\u2010AAG vector, we engineered an optimised bioproduction platform. By integrating a GFP\u2010HRV3C fusion tag system with affinity purification and subsequent proteolytic cleavage, we achieved the high\u2010yield synthesis of recombinant human interferons (IFN\u2010\u03b11b and IFN\u2010\u03b12b) in\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    and\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Nicotiana tabacum<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u2018Xanthi\u2019. Codon optimisation of the cargo genes further enhanced protein accumulation, achieving yields of up to 55.2\u2009\u03bcg\/g fresh leaf weight. Taken together, these results provide new insights into how synonymous substitutions influence potyviral pathogenicity and validate the symptomless P1\u2010AAG vector as a robust system for biomanufacturing value\u2010added proteins.\n                  <\/jats:p>","DOI":"10.1111\/mpp.70304","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:20:37Z","timestamp":1782400837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of a Synonymous Mutation at Codon 178 in\n                    <scp>P1<\/scp>\n                    That Attenuates Potato Virus Y\u2010Induced Tobacco Vein Necrosis and Its Application for Expressing Human Interferon"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0901-5907","authenticated-orcid":false,"given":"De\u2010Guo","family":"Liu","sequence":"first","affiliation":[{"name":"College of Plant Protection Shandong 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