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-κB) signaling pathway and the intracellular upregulation of NF-κB signaling can induce an antiviral effect. Therefore, the association between the inhibition of HBV replication by MyD88 and NF-κB activation was investigated further. The results show that NF-κB activation was moderately increased after MyD88 expression. The strong activation of NF-κB by the IkappaB kinase complex IKKα/IKKβ dramatically suppressed HBV replication; the MyD88 dominant negative mutant that abrogated NF-κB activity did not inhibit HBV replication. Furthermore, the IκBα dominant negative mutant restored the inhibition of HBV replication by MyD88. These results support a role for NF-κB activation in the inhibition of HBV replication and suggest a novel mechanism for the inhibition of HBV replication by MyD88 protein.