Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses

TLDR

RNase L is an antiviral enzyme activated by 2′,5′‑oligoadenylates produced by interferon‑induced OAS proteins in response to viral dsRNA, but it was unclear which OAS is essential for its activation. OAS3, but not OAS1 or OAS2, is required for RNase L activation and limits replication of four human viruses, suggesting OAS3 as a potential antiviral target while OAS1/2 may have other roles.

Abstract

Significance RNase L, an antiviral enzyme activated during infection, degrades viral and cellular RNAs, inhibits protein synthesis, and restricts the replication and spread of diverse viruses. RNase L activation depends on 2′,5′-oligoadenylates synthesized by different oligoadenylate synthetases (OASs), i.e., OAS1, OAS2, and OAS3. OASs are induced by interferon and are activated by viral dsRNA. It has been unclear which of these OAS proteins is necessary and/or sufficient to activate RNase L during viral infections. We show that OAS3, but not OAS1 or OAS2, is required to activate RNase L and to restrict the replication of four different human viruses. These findings suggest that OAS3 may provide a target for antiviral therapies and that OAS1 and OAS2 may have alternative roles.