Hepatitis B virus sensitizes hepatocytes to complement-dependent cytotoxicity through downregulating CD59.
Hepatitis B virus sensitizes hepatocytes to complement-dependent cytotoxicity through downregulating CD59.
复制标题
DOI：
10.1016/j.molimm.2009.09.022
复制
发表时间：
2009-12
影响因子：
3.6
通讯作者：
Z. Qu;Xiao-hong Liang;Yugang Liu;Juan Du;Suxia Liu;Wensheng Sun
中科院分区：
文献类型：
--
作者：
Z. Qu;Xiao-hong Liang;Yugang Liu;Juan Du;Suxia Liu;Wensheng Sun
B型肝炎病毒（HBV）感染困扰着全世界超过3.5亿人，并且是肝炎、肝硬化和肝细胞癌的主要原因。HBV在肝细胞中非致细胞病变地复制，并且大多数肝损伤是由对病毒的免疫应答引起的。虽然大多数研究集中在获得性免疫应答，先天免疫应答，特别是补体激活，在HBV感染中的作用仍然不清楚。为了确定参与HBV感染发病机制的蛋白质，我们进行了基因芯片分析，比较HBV转基因BALB/c小鼠与对照小鼠的基因表达谱。CD 59 mRNA在HBV转基因肝细胞中表达显著下调，RT-PCR和real-time PCR进一步证实了这一结果。为了探讨CD 59与HBV感染之间的关系，我们检测了HBV对两种肝细胞系中CD 59表达和补体依赖性细胞溶解的影响。我们发现，HBV可以显着下调CD 59的表达和敏感的细胞补体依赖性裂解。使用CD 59特异性抗体阻断CD 59功能大大降低了HBV效应。在慢性HBV感染患者的肝脏中也观察到类似的CD 59下调。这些结果表明，HBV可以通过下调CD 59使肝细胞对补体依赖性细胞毒性（CDC）敏感，这可能导致补体系统的激活并引起肝脏炎症。
Hepatitis B virus (HBV) infection afflicts over 350 million people worldwide and is a leading cause of hepatitis, cirrhosis and hepatocellular carcinoma. HBV replicates noncytopathically in hepatocytes, and most of the hepatic injury is caused by the immune response to the virus. While most studies focused on the adaptive immune response, the role of the innate immune response, especially the complement activation, in HBV infection remains obscure. To identify proteins that are involved in the pathogenesis of HBV infection, we carried out gene microarray analysis to compare the gene expression profile of HBV transgenic BALB/c mice with that of control mice. CD59 mRNA, which encodes an important complement regulatory protein (CRP) expressed on cell surface, was found to be significantly downregulated in HBV transgenic liver, a result that was further confirmed by RT-PCR and real-time PCR. To explore the relationship between CD59 and HBV infection, we examined the effect of HBV on CD59 expression and complement-dependent cytolysis in two hepatocyte cell lines. We found that HBV could significantly downregulate CD59 expression and sensitize cells to complement-dependent lysis. Blocking CD59 function using a CD59-specific antibody greatly diminished the HBV effect. Similar CD59 downregulation was also observed in the livers of patients with chronic HBV infection. These results demonstrate that HBV can sensitize hepatocytes to complement-dependent cytotoxicity (CDC) through downregulating CD59, which may lead to the activation of complement system and cause liver inflammation.