Ohio State University, Columbus

Cleaved/activated caspase-8 was observed in the transfected cells but there was not expression of Bcl-2 indicated that ORF3a may have a pro-apoptotic function by affecting the extrinsic and not the intrinsic apoptotic pathway. 

The Role of ORF3a protein in apoptosis of host cells: Caspase-8 and Bcl-2

Cytochrome C, t-Bid, and cleaved/activated caspase-9 were observed in cells with expressed ORF3a and that if an inhibitor was used that inhibited the function of either caspase-8 or caspase-9, there was a drastic reduction in apoptosis of cells with the ORF3a protein. This further cements the proposition that ORF3a plays a role in triggering the extrinsic apoptotic pathway as well as the mechanism that links the death receptor signaling and mitochondrion-dependent apoptosis.

The Role of ORF3a protein in apoptosis of host cells: Other Molecules of Mitochondrion-dependent Apoptosis

Ren, Y., Shu, T., Wu, D. et al. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cell Mol Immunol 17, 881–883 (2020). https://doi.org/10.1038/s41423-020-0485-9

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