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.
【초록키워드】 COVID-19, SARS-CoV-2, viral infection, ACE2, Gene Expression, hypoxia, Influenza, interferon, SARS-CoV-2 virus, virus, viral infections, SARS-CoV-2 receptor, Nasopharyngeal swab, RT-qPCR, infections, Viral, Viral load, nasopharyngeal, qPCR, Patient, epithelial cells, receptor, correlation, cell death, ACE2 expression, expression, mild symptoms, COVID-19 patients, host gene expression, Nasopharyngeal swab samples, association, antiviral response, COVID-19 patient, L-DOPA, EPO, Regulation, tissue, infected cells, infected individuals, enrichment, individual, favor, SARS-CoV-2-infected cells, VeroE6 cells, SARS-CoV-2-infected individuals, nasopharyngeal swab sample, mRNA levels, ENCODE, while, interferon-stimulated gene, cultured virus, influenza-infected patients, mRNA level, cell population, isoform, Host, Effect, non-infected, whole blood sample, analyzed, Sample, significantly, evaluated, elevated, subjects, in viral, correlated, suppresse, individuals, statistically significant, co-expressed, quantified, DDC, hours post-infection, negatively affected, the SARS-CoV-2, 【제목키워드】 ACE2, SARS-COV-2 infection, expression, association, alteration, isoform,