Rotavirus Controls Activation of the 2'-5'-Oligoadenylate Synthetase/RNase L Pathway Using at Least Two Distinct Mechanisms.

Rotaviruses represent an important cause of severe gastroenteritis in the young of many animal species, including humans. In this work, we have found that the OAS/RNase L pathway is activated during rotavirus infection, but the virus uses two different strategies to prevent the deleterious effects of this innate immune response of the cell. Early during virus entry, the initial interactions of the viral particle with the cell result in the inhibition of RNase L activity during the first hours of the infection. Later on, once viral proteins are synthesized, the phosphodiesterase activity of VP3 degrades the cellular 2'-5'-oligoadenylates, which are potent activators of RNase L, preventing its activation. This work demonstrates that the OAS/RNase L pathway plays an important role during infection and that the phosphodiesterase activity of VP3 is relevant during the replication cycle of the virus.