Post-translational modifications of coronavirus proteins: roles and function

Fung, To Sing; Liu, Ding Xiang

Coronavirus nsp16 has been identified as a nucleoside-2 O-methyltransferase (2 -O-MTase) [156] . By modifying the cap-0 structure at the ribose 2 -O position of the first nucleotide to form cap-1 structures, nsp16 enables the viral RNA to avoid detection by the cytoplasmic pattern recognition receptor MDA5. In fact, compared with wild-type control, recombinant virus lacking the nsp16 2 -O-MTase activity induced a high level of type I interferon in the infected cells, and viral replication was highly sensitive to the antiviral function of exogenous interferon [157] . Using yeast two-hybrid screening, a component of E3 ubiquitin ligase -von Hippel Lindau (VHL) was found to interact with SARS-CoV nsp16 [158] . Overexpression of VHL promoted the ubiquitin-proteasomal degradation of SARS-CoV nsp16, while knockdown of VHL increased the protein stability of nsp16 [158] . However, the precise ubiquitination site in SARS-CoV nsp16 has not been mapped, and similar modifications of nsp16 in other coronaviruses have not been characterized. Also, the physiological significance of nsp16 ubiquitination remains to be investigated using recombinant viruses under the setting of actual coronavirus infection.