Antisense Oligonucleotides Targeting Abhydrolase Domain Containing 2 Block Human Hepatitis B Virus Propagation
Antisense Oligonucleotides Targeting Abhydrolase Domain Containing 2 Block Human Hepatitis B Virus Propagation
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DOI：
10.1089/oli.2011.0280
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发表时间：
2011-04-01
期刊：
影响因子：
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通讯作者：
Wang, Shengqi
中科院分区：
文献类型：
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作者：
Ding, Xiaoran;Yang, Jing;Wang, Shengqi
B型肝炎病毒（HBV）感染是世界范围内的主要健康问题，只有少数接受治疗的患者在短期治疗后产生持续的保护性应答，大多数患者需要长期治疗以抑制病毒复制。然而，最近的一些报道表明，抑制某些宿主细胞蛋白质可以防止病毒感染，特别是我们以前的研究已经证实了人abhydrolase domain containing 2（ABHD 2）在HepG2.2.15细胞中上调，但被拉米夫定下调。这些观察结果表明，ABHD 2是重要的HBV传播，并可能成为一个新的抗HBV药物的目标。为了评估ABHD 2在HBV感染过程中的重要性，使用反义寡核苷酸（ASODN）下调HepG2.2.15细胞中ABHD 2的表达。在5个ASODNS候选者中，AB3显著下调ABHD2 mRNA和蛋白表达水平。此外，AB 3显著降低细胞培养基中HBV DNA、B型肝炎表面抗原和B型肝炎“e”抗原蛋白表达水平，而不影响细胞活力。这些结果表明，使用ASODN下调ABHD2阻断HBV复制和表达，而不影响宿主细胞生理学。此外，数据表明ABHD2在HBV传播中的重要作用，表明它可以作为抗HBV药物开发的新靶点。
Hepatitis B virus (HBV) infection is a major health concern worldwide and only a minority of treated patients develop a sustained protective response following a short course of therapy, and most patients require prolonged treatment to suppress viral replication. However, several recent reports showed that inhibition of certain host cell proteins prevented viral infection, specifically the human abhydrolase domain containing 2 (ABHD2) has been confirmed by our previous study to be upregulated in HepG2.2.15 cells but downregulated by lamivudine. These observations suggested that ABHD2 was important for HBV propagation and could be a target of novel anti-HBV drugs. To assess the importance of ABHD2 to the HBV infection process, antisense oligonucleotides (ASODNs) were used to downregulate ABHD2 expression in HepG2.2.15 cells. From 5 ASODNS candidates tested, AB3 significantly downregulated ABHD2 mRNA and protein expression levels. Further, AB3 significantly reduced HBV DNA, hepatitis B surface antigen, and hepatitis B "e'' antigen protein expression levels in cell medium without affecting cell viability. These results suggest that downregulation of ABHD2 using ASODNs blocked HBV replication and expression without affecting host cell physiology. Further, data demonstrated an essential role of ABHD2 in HBV propagation, suggesting it can serve as a novel target for anti-HBV drug development.