RNase L is a well-known effector of the type I interferon pathway. This review focuses on the recent developments of RNase L activation and on the antagonism of the OAS-RNase L pathway by viral proteins. Recent structural data show that two 2'-5' oligoadenylate molecules can bridge ankyrin domains of two RNase L subunits bound in opposite orientations. The binding of nucleotides to the pseudokinase domain further strengthens the dimer and imparts an active conformation to the ribonuclease. The OAS/RNase L pathway is active against many viruses and viruses evolved in several ways to escape this pathway. Influenza virus A acts upstream of this pathway by hiding double stranded RNA through its NS1 protein. In this way, it also inhibits the PKR and TLR-3 activation by double stranded RNA. Theiler's virus acts downstream of the OAS/RNase L pathway, through the direct interaction between protein L* and RNase L. By acting on the effector enzyme, Theiler's virus ensures a strong RNase L inhibition, which seems to be particularly useful for the infection of macrophages. In conclusion, viruses have developed distinct strategies to escape RNase L activity, that are likely dependent on their tropism. The fact that viral proteins have evolved to specifically antagonize RNase L outlines the importance of this particular IFN effector in cells infected by those viruses.
Keywords: RNase L; anti-viral defense; innate immunity; interferon; oligoadenylate synthetase.