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-kappaB) signaling pathway and the intracellular upregulation of NF-kappaB signaling can induce an antiviral effect. Therefore, the association between the inhibition of HBV replication by MyD88 and NF-kappaB activation was investigated further. The results show that NF-kappaB activation was moderately increased after MyD88 expression. The strong activation of NF-kappaB by the IkappaB kinase complex IKKalpha/IKKbeta dramatically suppressed HBV replication; the MyD88 dominant negative mutant that abrogated NF-kappaB activity did not inhibit HBV replication. Furthermore, the IkappaBalpha dominant negative mutant restored the inhibition of HBV replication by MyD88. These results support a role for NF-kappaB activation in the inhibition of HBV replication and suggest a novel mechanism for the inhibition of HBV replication by MyD88 protein.
Lin
Shanshan
S
Laboratory of Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wu
Min
M
Xu
Yang
Y
Xiong
Wei
W
Yi
Zhigang
Z
Zhang
Xiaonan
X
Zhenghong
Yuan
Y
D045744:Cell Line, Tumor; D005799:Genes, Dominant / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000502:physiology*; D009154:Mutation / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human