10.1371/journal.ppat.1006989 Melissa Drappier Melissa Drappier Babal Kant Jha Babal Kant Jha Sasha Stone Sasha Stone Ruth Elliott Ruth Elliott Rong Zhang Rong Zhang Didier Vertommen Didier Vertommen Susan R. Weiss Susan R. Weiss Robert H. Silverman Robert H. Silverman Thomas Michiels Thomas Michiels A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L Public Library of Science 2018 binding MHV OAS IFN protein chimeric mouse hepatitis virus 2-5 RNase L inhibition data show TMEV RNase L best-characterized effector pathways 2018-04-13 17:45:48 Dataset https://plos.figshare.com/articles/dataset/A_novel_mechanism_of_RNase_L_inhibition_Theiler_s_virus_L_protein_prevents_2-5A_from_binding_to_RNase_L/6141347 <div><p>The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L <i>in vivo</i>. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.</p></div>