Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

George Mpekoulis (1) , Efseveia Frakolaki (1) , Styliani Taka (2) , Anastasios Ioannidis (3) , Alice Vassiliou (2) , Katerina Kalliampakou (1) , Kostas Patas (4) , Ioannis Karakasiliotis (5) , Vassilis Aidinis (6) , Stylianos Chatzipanagiotou (2) , Emmanouil Angelakis (1, 7) , Dido Vassilacopoulou (2) , Niki Vassilaki (1)

1 Institut Pasteur Hellénique
2 NKUA - National and Kapodistrian University of Athens
3 University of Peloponnese
4 University of Athens Medical School [Athens]
5 DUTH - Democritus University of Thrace
6 Alexander Fleming Biomedical Sciences Research Center
7 VITROME - Vecteurs - Infections tropicales et méditerranéennes

L-Dopa decarboxylase ( DDC ) is the most significantly co-expressed gene with ACE2 , which encodes for the SARS-CoV-2 receptor a ngiotensin- c onverting e nzyme 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, p<0.001) and EPO (r≤−0.5, p<0.05). Moreover, a statistically significant correlation between DDC and dACE2 expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (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.

Mots clés: SARS CoV 2; COVID 19; Hypoxia; Respiratory infections; Epithelial cells; Gene expression; Viral load; Virus testing

Domaines: Bactériologie; Virologie; Parasitologie; Cardiologie et système cardiovasculaire; Maladies émergentes; Maladies infectieuses

George Mpekoulis, Efseveia Frakolaki, Styliani Taka, Anastasios Ioannidis, Alice Vassiliou, et al.. Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform. PLoS ONE, 2021, 16 (6), pp.e0253458. ⟨10.1371/journal.pone.0253458⟩. ⟨hal-03334348⟩