| Summary: | 碩士 === 國立成功大學 === 微生物及免疫學研究所 === 93 === A novel coronavirus has been identified as the etiologic agent of severe acute respiratory syndrome (SARS). Among the 14 potential open reading frames (ORFs) in its genome, several group-specific accessory proteins may be encoded. SARS coronavirus (SARS-CoV) ORF3 gene is a tricistronic ORF, which expresses 3a, 3b, and small envelope (SE) proteins. Though the 3a and SE proteins are known to be expressed during SARS-CoV infection, the role of these proteins in viral pathogenesis is still unknown. In the present study, we cloned the full-length ORF3 gene, including 3a, 3b, and SE, and transfected it into several lung epithelial cell lines. We found that expression of SARS-CoV ORF3 gene caused a general down-regulation of proteins synthesis. Next, we transfected three ORF3-encoded genes individually, and found that they used different mechanisms to shutdown cellular protein synthesis. First, 3a protein can localize to ER and Golgi apparatus and induced an ER stress response, possibly by forming calcium channel to release the ER-sequestrated calcium. Second, expression of 3b protein can lead to cell death, which may therefore shut-off cell metabolism. Finally, SE protein may be a potential “viroporin” and increase the intracellular sodium concentration, thus inhibiting protein translation by this “saline stress”. In conclusion, our findings suggest that these accessory molecules of SARS-CoV may play important roles during the virus life cycle and determinate viral virulence.
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