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绿僵菌变种dcjhyium的粗产棒曲霉素对乙型肝炎病毒基因表达和复制的抑制作用

Inhibition of hepatitis B virus gene expression & replication by crude destruxins from Metarhizium anisopliae var. dcjhyium.

作者信息

Dong Cong, Yu Jiuru, Zhu Ying, Dong Changjin

机构信息

State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan, Hubei Province, China.

College of Life Science, Hubei Normal University, Huangshi, Hubei Province, China.

出版信息

Indian J Med Res. 2013 Dec;138(6):969-76.

Abstract

BACKGROUND & OBJECTIVES: Destruxin A, destruxin B and destruxin E isolated from entomopathogenic fungus Metarhizium anisopliae showed a strong suppressive effect on the replication of hepatitis B virus (HBV) in human hepatoma cells. In this study, the anti-HBV effects of the crude destruxins extracted from M. anisopliae var. dcjhyium were detected both in vitro and in vivo.

METHODS

HepG2.2.15 cells were cultured to observe the inhibitory effects of the crude destruxins on the gene expression and replication of HBV by radioimmunoassay detection and real-time quantitative PCR. In vivo, duck HBV (DHBV)-infected ducks were treated with the crude destruxins at 2.0, 4.0, 6.0 μg/kg once a day for 15 days, DHBV DNA was examined by real-time quantitative PCR.

RESULTS

The crude destruxins suppressed the replication of HBV-DNA and the production of HBsAg and HBeAg with IC 50 of about 1.2 and 1.4 μg/ml. Transcript of viral mRNA was significantly suppressed by the crude destruxins in HepG2.2.15 cells. In vivo, the duck serum DHBV-DNA levels were markedly reduced in the group of the crude destruxins.

INTERPRETATION & CONCLUSIONS: The crude destruxins inhibited the gene expression and replication of HBV both in vitro and in vivo, and their anti-HBV effect was stronger than that with destruxin B. Our results indicate that the crude destruxins from M.anisopliae var. dcjhyium may be potential antivirus agents. Further studies need to be done to confirm these findings.

摘要

背景与目的

从昆虫病原真菌绿僵菌中分离出的 destruxin A、destruxin B 和 destruxin E 对人肝癌细胞中乙型肝炎病毒(HBV)的复制具有强烈的抑制作用。本研究检测了从绿僵菌变种 dcjhyium 中提取的粗提 destruxins 在体外和体内的抗 HBV 作用。

方法

培养 HepG2.2.15 细胞,通过放射免疫分析检测和实时定量 PCR 观察粗提 destruxins 对 HBV 基因表达和复制的抑制作用。在体内,用粗提 destruxins 以 2.0、4.0、6.0 μg/kg 的剂量每天一次处理感染鸭乙型肝炎病毒(DHBV)的鸭子,持续 15 天,通过实时定量 PCR 检测 DHBV DNA。

结果

粗提 destruxins 抑制 HBV-DNA 的复制以及 HBsAg 和 HBeAg 的产生,IC50 约为 1.2 和 1.4 μg/ml。粗提 destruxins 显著抑制 HepG2.2.15 细胞中病毒 mRNA 的转录。在体内,粗提 destruxins 组的鸭血清 DHBV-DNA 水平明显降低。

解读与结论

粗提 destruxins 在体外和体内均抑制 HBV 的基因表达和复制,其抗 HBV 作用强于 destruxin B。我们的结果表明,绿僵菌变种 dcjhyium 的粗提 destruxins 可能是潜在的抗病毒药物。需要进一步研究来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/3978990/98b72e328518/IJMR-138-969-g002.jpg

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