tailieunhanh - Báo cáo y học: "Hepatitis B virus core protein with hot-spot mutations inhibit MxA gene transcription but has no effect on inhibition of virus replication by interferon a"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Hepatitis B virus core protein with hot-spot mutations inhibit MxA gene transcription but has no effect on inhibition of virus replication by interferon a | Zhijian et al. Virology Journal 2010 7 278 http content 7 1 278 VIROLOGY JOURNAL RESEARCH Open Access Hepatitis B virus core protein with hot-spot mutations inhibit MxA gene transcription but has no effect on inhibition of virus replication by interferon a Yu Zhijian1 Huang Zhen1 Zhang Fan2 Yang Jin1 Deng Qiwen1 Zeng Zhongming1 Abstract 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 pro-teins L60V or S87G . However in Huh7 cells stably expressing WT or the mutated HBc proteins L60V S87G or I97L IFN-a 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 especial 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-a in Huh7 cells. The clinical significance of the inhibitory effect of MxA gene transcription by HBc protein requires further study. Introduction Many studies have indicated that hepatitis B virus HBV core gene mutations are significantly associated with hepatitis activity in patients with chronic hepatitis B CHB 1-4 . In addition gene mutations in the pre-core core region of HBV occur more frequently in patients with severe or fulminant hepatitis compared to asymptomatic carriers and those with acute self-limited hepatitis 1-3 . .