{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:22:21Z","timestamp":1781835741897,"version":"3.54.5"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"crossref","award":["URGENCE COVID-19"],"award-info":[{"award-number":["URGENCE COVID-19"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hellenic Pasteur Institute","award":["Excellence PhD fellowship"],"award-info":[{"award-number":["Excellence PhD fellowship"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>L-Dopa decarboxylase (<jats:italic>DDC<\/jats:italic>) is the most significantly co-expressed gene with <jats:italic>ACE2<\/jats:italic>, which encodes for the SARS-CoV-2 receptor <jats:underline>a<\/jats:underline>ngiotensin-<jats:underline>c<\/jats:underline>onverting <jats:underline>e<\/jats:underline>nzyme <jats:underline>2<\/jats:underline> and the interferon-inducible truncated isoform <jats:italic>dACE2<\/jats:italic>. Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate <jats:italic>DDC<\/jats:italic> expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with <jats:italic>ACE2<\/jats:italic> and <jats:italic>dACE2<\/jats:italic>. We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene <jats:italic>ISG56<\/jats:italic> and the immune-modulatory, hypoxia-regulated gene <jats:italic>EPO<\/jats:italic>. Viral load and mRNA levels of <jats:italic>DDC<\/jats:italic>, <jats:italic>ACE2<\/jats:italic>, <jats:italic>dACE2<\/jats:italic>, <jats:italic>ISG56<\/jats:italic> and <jats:italic>EPO<\/jats:italic> were quantified by RT-qPCR in nasopharyngeal swab samples from COVID-19 patients, showing no or mild symptoms, and from non-infected individuals. Samples from influenza-infected patients were analyzed in comparison. SARS-CoV-2-mediated effects in host gene expression were validated in cultured virus-permissive epithelial cells. We found substantially higher gene expression of <jats:italic>DDC<\/jats:italic> in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. <jats:italic>dACE2<\/jats:italic> was more elevated (2.9-fold; p = 1.02e-16) than <jats:italic>ACE2<\/jats:italic> (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. <jats:italic>ISG56<\/jats:italic> (2.5-fold; p = 3.01e-6) and <jats:italic>EPO<\/jats:italic> (2.6-fold; p = 2.1e-13) were also increased. Detected differences were not attributed to enrichment of specific cell populations in nasopharyngeal tissue. While SARS-CoV-2 virus load was positively associated with <jats:italic>ACE2<\/jats:italic> expression (r\u22650.8, p&lt;0.001), it negatively correlated with <jats:italic>DDC<\/jats:italic>, <jats:italic>dACE2<\/jats:italic> (r\u2264\u22120.7, p&lt;0.001) and <jats:italic>EPO<\/jats:italic> (r\u2264\u22120.5, p&lt;0.05). Moreover, a statistically significant correlation between <jats:italic>DDC<\/jats:italic> and <jats:italic>dACE2<\/jats:italic> expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (r\u22650.7). In VeroE6 cells, SARS-CoV-2 negatively affected <jats:italic>DDC<\/jats:italic>, <jats:italic>ACE2<\/jats:italic>, <jats:italic>dACE2<\/jats:italic> and <jats:italic>EPO<\/jats:italic> mRNA levels, and induced cell death, while <jats:italic>ISG56<\/jats:italic> was enhanced at early hours post-infection. Thus, the regulation of <jats:italic>DDC<\/jats:italic>, <jats:italic>dACE2<\/jats:italic> and <jats:italic>EPO<\/jats:italic> expression in the SARS-CoV-2-infected nasopharyngeal tissue is possibly related with an orchestrated antiviral response of the infected host as the virus suppresses these genes to favor its propagation.<\/jats:p>","DOI":"10.1371\/journal.pone.0253458","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T17:25:06Z","timestamp":1624987506000},"page":"e0253458","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform"],"prefix":"10.1371","volume":"16","author":[{"given":"George","family":"Mpekoulis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efseveia","family":"Frakolaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Styliani","family":"Taka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Ioannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-0476","authenticated-orcid":true,"given":"Alice G.","family":"Vassiliou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina 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