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>