Inhibition of hepatitis B virus replication by MyD88 involves accelerated degradation of pregenomic RNA and nuclear retention of pre-S/S RNAs.
Myeloid differentiation primary response protein 88 (MyD88), which can be induced by alpha interferon (IFN-alpha), has an antiviral activity against the hepatitis B virus (HBV). The mechanism of this antiviral activity remains poorly understood. Here, we report that MyD88 inhibited HBV replication in HepG2.2.15 cells and in a mouse model. The knockdown of MyD88 expression weakened the IFN-alpha-induced inhibition of HBV replication. Furthermore, MyD88 posttranscriptionally reduced the levels of viral RNA. Remarkably, MyD88 accelerated the decay of viral pregenomic RNA in the cytoplasm. Mapping analysis showed that the RNA sequence located in the 5'-proximal region of the pregenomic RNA was critical for the decay. In addition, MyD88 inhibited the nuclear export of pre-S/S RNAs via the posttranscriptional regulatory element (PRE). The retained pre-S/S RNAs were shown to degrade in the nucleus. Finally, we found that MyD88 inhibited the expression of polypyrimidine tract-binding protein (PTB), a key nuclear export factor for PRE-containing RNA. Taken together, our results define a novel antiviral mechanism against HBV mediated by MyD88.
Li
Jianhua
J
Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Lin
Shanshan
S
Chen
Qiying
Q
Peng
Lu
L
Zhai
Jianwei
J
Liu
Yinghui
Y
Yuan
Zhenghong
Z
D000818:Animals; D002460:Cell Line; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology / Q000821:virology; D006801:Humans; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism*; D014779:Virus Replication
C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012367:RNA, Viral
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