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10.1371/journal.pone.0253458

http://scihub22266oqcxt.onion/10.1371/journal.pone.0253458
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34185793!8241096!34185793
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suck abstract from ncbi


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pmid34185793      PLoS+One 2021 ; 16 (6): e0253458
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  • Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform #MMPMID34185793
  • Mpekoulis G; Frakolaki E; Taka S; Ioannidis A; Vassiliou AG; Kalliampakou KI; Patas K; Karakasiliotis I; Aidinis V; Chatzipanagiotou S; Angelakis E; Vassilacopoulou D; Vassilaki N
  • PLoS One 2021[]; 16 (6): e0253458 PMID34185793show ga
  • L-Dopa decarboxylase (DDC) is the most significantly co-expressed gene with ACE2, which encodes for the SARS-CoV-2 receptor angiotensin-converting enzyme 2 and the interferon-inducible truncated isoform dACE2. Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate DDC expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with ACE2 and dACE2. We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene ISG56 and the immune-modulatory, hypoxia-regulated gene EPO. Viral load and mRNA levels of DDC, ACE2, dACE2, ISG56 and EPO 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 DDC in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. dACE2 was more elevated (2.9-fold; p = 1.02e-16) than ACE2 (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. ISG56 (2.5-fold; p = 3.01e-6) and EPO (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 ACE2 expression (r>/=0.8, p<0.001), it negatively correlated with DDC, dACE2 (r/=0.7). In VeroE6 cells, SARS-CoV-2 negatively affected DDC, ACE2, dACE2 and EPO mRNA levels, and induced cell death, while ISG56 was enhanced at early hours post-infection. Thus, the regulation of DDC, dACE2 and EPO 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.
  • |Adaptor Proteins, Signal Transducing/genetics/metabolism[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/*metabolism[MESH]
  • |Area Under Curve[MESH]
  • |Aromatic-L-Amino-Acid Decarboxylases[MESH]
  • |COVID-19/*pathology/virology[MESH]
  • |Dopa Decarboxylase/genetics/*metabolism[MESH]
  • |Down-Regulation[MESH]
  • |Epithelial Cells/cytology/metabolism[MESH]
  • |Erythropoietin/genetics/metabolism[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Nasopharynx/metabolism[MESH]
  • |Protein Isoforms/genetics/metabolism[MESH]
  • |RNA-Binding Proteins/genetics/metabolism[MESH]
  • |ROC Curve[MESH]
  • |SARS-CoV-2/genetics/isolation & purification[MESH]
  • |Up-Regulation[MESH]


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