Figure 1. Viral PDE antagonism of OAS-RNase L.

(1) OAS proteins sense viral dsRNA upon infection and synthesize 2’-5’ oligoadenylate (2–5A) by linking ATP molecules via the 2’ and 5’ carbons. (2) 2–5A binds RNase L monomers, inducing homodimerization and activation (3A) Viral PDEs prevent RNase L activation by cleavage of 2–5A, facilitating viral replication (3B) In the absence of a functional PDE RNase L is activated and cleaves both viral and cellular ssRNA, restriction viral replication, inducing translational arrest, and ultimately resulting in cell death.