Question

Other coronaviruses such as SARS-CoV and MERS-CoV are known suppressors of Type I IFNs. Presumably, SARS-CoV-2 employs similar strategies. Explain how SARS-CoV and MERS-CoV may interfere with Type I IFN production and signaling through their receptors.

Answer 1

Ans

The SARS- CoV infere with the type 1 IFN production The nucleocapsid protein calledN protein of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production.

Type I IFN production induced by poly I·C or Sendai virus was suppressed by the SARS-CoV N protein. This provide an interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein.

Middle East respiratory syndrome coronavirus inhibits type I interferon production through both cytoplasmic and nuclear targets

Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which contribute to MERS-CoV pathogenesis.

The ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production.

Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β and ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. These results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism.