Impaired antiviral response due to up‐regulated HSCARG and down‐regulated NF‐κB signaling by HCoV 229E infection in G6PD‐knockdown A549 cells

Glucose‐6‐phosphate dehydrogenase (G6PD) provides NADPH as reducing power for maintenance of the cellular redox status. Previously, we have reported that G6PD‐deficient cells are more susceptible to viral infection, however, the mechanism remains elusive. Toward this end, we analyzed the antiviral response upon HCoV 229E infection in A549 and MRC‐5 cells and found that the expression of TNFα, OAS and MX‐1 genes were up‐regulated at the early stage of viral infection. We further investigated the mRNA expression of OAS and MX‐1 was slightly decreased in G6PD‐knockdown cells. In addition, the expression of antiviral cytokine, TNFα, was lower in G6PD‐knockdown than that in control cells. Interestingly, the reduced antiviral responses in G6PD‐knockdown cells could be restored by complementation of G6PD activity. In addition, reduced IκB degradation and decreased NFκB activation were observed in G6PD‐knockdown A549 cells when compared with that of control. Furthermore, we found that HSCARG protein which was the NADPH sensor and could hamper NFκB activation was up‐regulated in G6PD‐knockdown A549 cells leading to impaired antiviral gene expression. All in all, these data support the notion that enhanced susceptibility to viral infection in G6PD‐knockdown cells is due to impaired NFκB signaling by redox imbalance‐induced increasing HSCARG expression and adversely affects the antiviral response.