Interferon-inducible MyD88 protein inhibits hepatitis B virus replication.
Myeloid differential primary response protein (MyD88) is a critical component in the signaling cascade through Toll-like receptors (TLRs) and is induced by alpha interferon (IFN-alpha). To examine the role of MyD88 in the antiviral activity of IFN-alpha against hepatitis B virus (HBV), we established MyD88 stably expressing cell lines and studied HBV replication in these lines after transient transfection. The levels of HBV proteins and viral replicative intermediates were effectively reduced in MyD88-expressing cells. A significant reduction of total and cytoplasmic viral RNAs in MyD88 stably expressing cells was also observed. Using a nuclear factor-kappaB (NF-kappaB) dependent reporter assay, it was shown that activation of NF-kappaB was moderately increased in the presence of expression of MyD88, and further significantly increased by co-expression of HBV. These results suggest a novel mechanism for the inhibition of HBV replication by IFN-alpha via expression of MyD88 protein involving activation of NF-kappaB signaling pathway and downregulation of viral transcription.
Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wei
W
Xiong
Xun
X
Wang
Xiaoying
X
Liu
Li
L
Xiang
Lingjie
L
Zheng
Zhenghong
Z
Yuan
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000502:physiology*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016898:Interferon-alpha; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic