Antimyogenic Effect of SARS-CoV Spike Protein in C2C12 Myoblasts

C2C12 myoblasts serve as well-established model system to study myogenesis, as they fuse to form multinucleated myotubes. Severe acute respiratory syndrome coronavirus (SARS–CoV) spike (S) protein plays a crucial role in viral entry. Exogenous expression of S protein in C2C12 myoblasts inhibits the formation of myotubes. Global changes in gene expression were studied in C2C12 cells expressing S protein using oligonucleotide microarray analysis. The expression profile showed that, most of the myogenic marker genes were downregulated. Next, we used RT-PCR analysis to reexamine some downregulated and upregulated genes. To further study the antimyogenic effects induced by the S protein, we introduced antisense Plf (proliferin), an upregulated gene, into the antimyogenic cells. Antisense Ace2 (angiotensin-converting enzyme 2), the cellular receptor of S protein, was also introduced into C2C12 myoblasts. Results indicated that antimyogenic effect induced by S protein was partially rescued in cells expressing antisense Plf, while C2C12 cells expressing antisense Ace2 showed upregulation of Plf.