Enterovirus 2C Protein Suppresses IKK Phosphorylation by Recruiting IKK and IKK into Viral Inclusion Bodies.

The nuclear factor-kappa B (NF-B) signaling network constitutes a first line of defense against the invading viruses. However, viruses also adopted multiple strategies to interfere with NF-B activation. Enterovirus 71 (EV71), in the family Picornaviridae, has become the main pathogen responsible for hand, foot, and mouth disease. Recent studies have reported that the nonstructural protein 2C of EV71 inhibits TNF- induced NF-B activation by suppressing IKK phosphorylation. In our study, we found that 2C can form inclusion bodies (IBs) in infected and transfected cells. Furthermore, 2C was able to sequester IKK into IBs through direct interaction with IKK. Although 2C did not directly interact with IKK, viral protein 2C was able to sequester the IKK into the IBs mediated by IKK. Our data further demonstrated that EV71 2C could suppress IKK phosphorylation. These all together support a novel mechanism for EV71 to escape from NF-B response, in which the phosphorylation of IKK was suppressed by being recruited into viral IBs in the presence of 2C and IKK.