Inhibition of hepatitis B virus replication by MyD88 is mediated by nuclear factor-kappaB activation

In our previous paper, we reported that myeloid differential primary response protein (MyD88), a key adaptor in the signaling cascade of the innate immune response, inhibits hepatitis B virus (HBV) replication. The MyD88 activated nuclear factor-kappaB (NF-kappa B) signaling pathway and the intracellular upregulation of NF-kappa B signaling can induce an antiviral effect. Therefore, the association between the inhibition of HBV replication by MyD88 and NF-kappa B activation was investigated further. The results show that NF-kappa B activation was moderately increased after MyD88 expression. The strong activation of NF-kappa B by the IkappaB kinase complex IKK alpha/IKK beta dramatically suppressed HBV replication; the MyD88 dominant negative mutant that abrogated NF-kappa B activity did not inhibit HBV replication. Furthermore, the I kappa B alpha dominant negative mutant restored the inhibition of HBV replication by MyD88. These results support a role for NF-kappa B activation in the inhibition of HBV replication and suggest a novel mechanism for the inhibition of HBV replication by MyD88 protein. 0 2007 Elsevier B.V. All rights reserved.