Identification of a Nidovirales Orf1a N7-guanine cap Methyltransferase signature-sequence as a genetic marker of large genome Tobaniviridae

François Ferron; Humberto Julio Debat; Etienne Decroly; Bruno Canard

The presence of a MTase in Nidovirales Orf1a is unexpected, and had not been reported before, although signature sequences of an uncharacterized MTase had been detected in Ball Python nidovirus, Sectovirus 1 and Infratovirus 1 [23] . Both protein and enzyme functions in Nidovirales have been classified into a functional triangle [21] , each side of the triangle representing a carrier of the following functions: Orf1a: host defence; Orf1b: genome maintenance; Orfs at the 3'-end: structural products. In this triangle, the MTase-type of activity involved in genome maintenance would usually map to Orf1b [21] . Perhaps indeed this MTase is involved in tasks other than RNA capping, which remain to be determined. Accordingly, it was recently reported that viral or cellular MTases can be recruited by viruses in order to induce internal methylation of their genome [45] and escape to the antiviral response mediated by MDA5 [46] . Out of the gain of this (still putative) enzyme activity in this virus group, the copy number of Orf1a products is expected to be 3-6 time higher than those of Orf1b, raising the following questions: why only these Tobaniviridae members need such additional MTase ? Why do they need it in high amounts, provided that the Orf1a stoichiometry is thought to be higher than that of Orf1b products? Are activity levels provided by this enzyme low? What is its actual substrate specificity?