Hepatitis B virus core protein with hot-spot mutations inhibit MxA gene transcription but has no effect on inhibition of virus replication by interferon α.
It has been reported that hepatitis B virus (HBV) core protein (HBc) can inhibit the transcription of human interferon-induced MxA gene. In this study, we investigated whether HBc protein mutations at hot spots (L60V, S87G and I97L) could still inhibit MxA transcription and the potential significance of this inhibition in virus replication in vitro. Our data indicated that the IFN-induced MxA mRNA expression level and MxA promoter activity was significantly down-regulated by mutant protein of HBc(I97L), compared to WT and the other two mutated HBc proteins(L60V or S87G). However, in Huh7 cells stably expressing WT or the mutated HBc proteins (L60V, S87G or I97L), IFN-α could inhibit the extra- and intracellular HBV DNA level and HBsAg secretion to a similar level compared to that in cells transfected with control plasmids. In conclusion, HBc protein with I97L mutation may play an special role in suppressing the transcription of MxA gene. Moreover, the inhibitory effect on MxA gene transcription by the WT or mutated HBc proteins (L60V, S87G and I97L) has no impact on inhibition of HBV replication by IFN-α in Huh7 cells. The clinical significance of the inhibitory effect of MxA gene transcription by HBc protein requires further study.
Zhijian
Yu
Y
Department of Infectious Diseases, the Affiliated Shenzhen Nanshan Hospital of Guangdong Medical College, Shenzhen, China.
Zhen
Huang
H
Fan
Zhang
Z
Jin
Yang
Y
Qiwen
Deng
D
Zhongming
Zeng
Z
D002460:Cell Line; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D020869:Gene Expression Profiling; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D020125:Mutation, Missense; D064547:Myxovirus Resistance Proteins; D014158:Transcription, Genetic; D014779:Virus Replication
D006512:Hepatitis B Core Antigens; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins