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, 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