Figure 6.

Viruses interfere with several stages of the RNase L pathway. RNase L is indirectly activated by the presence of double‐stranded RNA (dsRNA) species in the cytoplasm of infected cells. dsRNA activates 2^′,5^′‐oligoadenylate synthetase (OAS), which produces 2^′‐5^′‐oligoadenylate (2–5A), an allosteric activator for RNase L (asterisks indicate active enzymes). The NS1 protein of influenza virus A prevents OAS activation, whereas vaccinia virus and HIV‐1 block activation of RNase L by 2–5A, the latter by decreasing the affinity of RNase L for its activator. Once activated, RNase L can cleave viral RNAs and also cellular mRNAs and rRNAs. Several viruses specifically protect their RNAs from degradation, including poliovirus (PV), hepatitis C virus (HCV), and possibly reoviruses, using their σ 3 protein. Reoviruses also exploit RNase L‐mediated destruction of cellular messages to decrease competition for gene expression machinery.