Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 153, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2021.112286
Keywords
Selenium; Selenoprotein; mRNA expression; SARS-CoV-2; COVID-19
Categories
Funding
- Emergency Research Project of Novel Coronavirus Infection of Anhui Province [202004a07020002, 202004a07020004]
- National Natural Science Foundation of China [31972459, 31771971]
- Key Research and Development Program of Anhui Province [1804b06020367, 201904b11020038]
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SARS-CoV-2 infection significantly suppressed the expression of a specific set of selenoprotein mRNAs in Vero cells, particularly affecting selenoproteins related to ferroptosis, DNA synthesis, and endoplasmic reticulum function.
Higher selenium status has been shown to improve the clinical outcome of infections caused by a range of evolutionally diverse viruses, including SARS-CoV-2. However, the impact of SARS-CoV-2 on host-cell selenoproteins remains elusive. The present study investigated the influence of SARS-CoV-2 on expression of selenoprotein mRNAs in Vero cells. SARS-CoV-2 triggered an inflammatory response as evidenced by increased IL-6 expression. Of the 25 selenoproteins, SARS-CoV-2 significantly suppressed mRNA expression of ferroptosisassociated GPX4, DNA synthesis-related TXNRD3 and endoplasmic reticulum-resident SELENOF, SELENOK, SELENOM and SELENOS. Computational analysis has predicted an antisense interaction between SARS-CoV-2 and TXNRD3 mRNA, which is translated with high efficiency in the lung. Here, we confirmed the predicted SARS-CoV-2/TXNRD3 antisense interaction in vitro using DNA oligonucleotides, providing a plausible mechanism for the observed mRNA knockdown. Inhibition of TXNRD decreases DNA synthesis which is thereby likely to increase the ribonucleotide pool for RNA synthesis and, accordingly, RNA virus production. The present findings provide evidence for a direct inhibitory effect of SARS-CoV-2 replication on the expression of a specific set of selenoprotein mRNAs, which merits further investigation in the light of established evidence for correlations between dietary selenium status and the outcome of SARS-CoV-2 infection.
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