{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:38:35Z","timestamp":1792618715932,"version":"4.5.0"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Plant Biotechnology Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    The production of coronavirus disease 2019 vaccines can be achieved by transient expression of the Spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 in agroinfiltrated leaves of\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    , a process promoted by the co\u2010expression of viral silencing suppressor P19. Upon expression, the S protein enters the cell secretory pathway, before being trafficked to the plasma membrane where formation of coronavirus\u2010like particles (CoVLPs) occurs. We recently used RNAseq and time course sampling to characterize molecular responses of\n                    <jats:italic>N.\u2009benthamiana<\/jats:italic>\n                    leaf cells expressing P19 only or P19 in combination with recombinant S protein. This revealed expression of the viral proteins to deeply affect the physiological status of plant cells, including through the activation of immune responses. Here, transcriptomics shows that the production of CoVLPs also induces leaf senescence, as revealed by the up\u2010regulation of senescence\u2010associated genes, activation of senescence\u2010related proteases and down\u2010regulation of genes involved in basic metabolic functions like photosynthesis or nitrogen uptake and assimilation. CoVLP production also up\u2010regulates asparagine synthetase genes and leads to the consequent accumulation of asparagine, a nitrogen\u2010rich amino acid known to facilitate reallocation of nitrogen resources from senescent to young growing organs. Hypothesizing these combined host responses to restrain foreign protein accumulation, an attempt was made to support nitrogen reduction in CoVLP\u2010producing leaves by co\u2010expressing a constitutively active, light\u2010insensitive form of nitrate reductase. We show this strategy to increase S protein accumulation in leaf tissues, thereby suggesting that boosting nitrogen metabolism in agroinfiltrated leaves may improve recombinant protein yields in\n                    <jats:italic>N.\u2009benthamiana<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/pbi.70154","type":"journal-article","created":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T09:04:13Z","timestamp":1749373453000},"page":"204-223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expression of a constitutively active nitrate reductase increases SARS\u2010CoV\u20102 Spike protein production in\n                    <i>Nicotiana benthamiana<\/i>\n                    leaves that otherwise show traits of senescence"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8289-4498","authenticated-orcid":false,"given":"Louis\u2010Philippe","family":"Hamel","sequence":"first","affiliation":[{"name":"Medicago Inc.  Montr\u00e9al QC Canada"},{"name":"Direction G\u00e9n\u00e9rale de la Recherche, des Programmes et des Partenariats Minist\u00e8re de l'Agriculture, des P\u00eacheries et de l'Alimentation du Qu\u00e9bec  Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010\u00c8ve","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Medicago Inc.  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Poirier\u2010Gravel","sequence":"additional","affiliation":[{"name":"Medicago Inc.  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Tardif","sequence":"additional","affiliation":[{"name":"Medicago Inc.  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc\u2010Andr\u00e9","family":"Comeau","sequence":"additional","affiliation":[{"name":"Medicago Inc.  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Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9ane","family":"Langlois","sequence":"additional","affiliation":[{"name":"Centre de recherche et d'innovation sur les v\u00e9g\u00e9taux, D\u00e9partement de phytologie Universit\u00e9 Laval  Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Claire","family":"Goulet","sequence":"additional","affiliation":[{"name":"Centre de recherche et d'innovation sur les v\u00e9g\u00e9taux, D\u00e9partement de phytologie Universit\u00e9 Laval  Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc\u2010Andr\u00e9","family":"D'Aoust","sequence":"additional","affiliation":[{"name":"Medicago Inc.  Montr\u00e9al QC Canada"},{"name":"Aramis Biotechnologies Inc.  Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-1142","authenticated-orcid":false,"given":"Dominique","family":"Michaud","sequence":"additional","affiliation":[{"name":"Centre de recherche et d'innovation sur les v\u00e9g\u00e9taux, D\u00e9partement de phytologie Universit\u00e9 Laval  Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.8.3.505"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2010.04151.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/mp\/ssq080"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants8110492"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.111.083345"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2005.02399.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nph.14676"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jipb.13434"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2024.1305855"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.105.060764"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)01300-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.15.00567"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plantsci.2010.04.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.34"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-313X.2003.01908.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2007.03226.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2004.10.008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.108.115741"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.106.079293"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.12852"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2006.02723.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3040.2003.01158.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43897-021-00006-9"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201300"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.14247"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.70075"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plantsci.2006.01.011"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2116623119"},{"key":"e_1_2_9_30_1","first-page":"2513","article-title":"Nitrogen remobilization during leaf senescence: lessons from Arabidopsis to crops","volume":"68","author":"Hav\u00e9 M.","year":"2017","journal-title":"J. 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