Hepatitis B virus sensitizes hepatocytes to complement-dependent cytotoxicity through downregulating CD59.
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.
Qu
Zhonghua
Z
Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
Liang
Xiaohong
X
Liu
Yugang
Y
Du
Juan
J
Liu
Suxia
S
Sun
Wensheng
W
D000818:Animals; D018957:CD59 Antigens / Q000276:immunology*; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000821:virology; D022781:Hepatocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D014162:Transfection
D018957:CD59 Antigens; D003165:Complement System Proteins