Broad-spectrum antiviral activity of Mycoplasma genitalium Ribonuclease R

Ribonuclease (RNase) is a hydrolase that catalyzes the cleavage of phosphodiesters in RNA. This study started from an RNase R from Mycoplasma (MgR), sensitive to 2-O-methylation (Nm). We confirmed that such sensitivity was evolved by SNP under selection, leading to a negligible effect on host cell growth and proliferation than other selected RNases. On the contrary, MgR hydrolyzed RNA from MHV-A59 more efficiently. Such bias was partially due to the difference of Am status in poly(A) tails of virus and host cells. Furthermore, with the help of the novel Nm identification tool NJU-Seq, we developed, Nm maps of MHV-A59 was drawn at base resolution for the first time and indicated multiple Nm sites in MHV-A59 genome and subgenomic RNAs but not anti-genome or anti-subgenomic RNAs, which suggested the latter may be the potential target of MgR during the virus replication. Further cell tests confirmed that MgR could inhibit multiple viruses (MCMV, AdV-5, MHV-A59) in different cell lines with little effect on host cells. Fused with the first three transmembrane domains (amino acids 1-87) of NSP6 of MHV had a significantly better inhibitory effect. In conclusion, this study demonstrated the broad-spectrum antiviral ability of MgR to DNA and RNA viruses, which provided a new direction to fight against viruses independent of a specific sequence or protein.