目的探讨杀伤细胞免疫球蛋白(KIR)及其配体人类白细胞抗原(HLA)基因的遗传多态性在发生乙肝病毒(HBV)相关性肝癌中的可能作用。方法回顾性分析56例HBV相关性HCC患者与503例健康志愿者的KIR和HLA基因型,探讨KIR基因型、KIR组合型以及KIR-...目的探讨杀伤细胞免疫球蛋白(KIR)及其配体人类白细胞抗原(HLA)基因的遗传多态性在发生乙肝病毒(HBV)相关性肝癌中的可能作用。方法回顾性分析56例HBV相关性HCC患者与503例健康志愿者的KIR和HLA基因型,探讨KIR基因型、KIR组合型以及KIR-HLA组合型与发生HBV相关性肝癌的相关性。结果比较分析发现,HCC组和对照组KIR基因频率之间的差异无统计学意义(P>0.05)。KIR与其配体HLA-Ⅰ的比较分析中发现,HCC组Bw4频率显著低于对照组(HCC vs control=53.6%vs 66.7%,P=0.05); HCC组2DL2/3+HLA-C1与3DL1+HLA-B Bw4通路的频率显著低于对照组(HCC vs control=67.8%vs 96.0%,P=0.00&HCC vs control=50.0%vs 64.2%,P=0.042)。对KIR基因与HBV-DNA载量关系的调查发现,高载量组中2DS5基因频率均显著高于中载量组和低载量组(High vs Middle=55.6%vs 14.3%,P=0.014&High vs Low 55.6%vs 19.2%,P=0.025)。结论 HCC组中表达KIR-AB3组合型、减少2DL2/3+HLA-C1与3DL1+HLA-B Bw4通路和表达KIR2DS5与NK细胞天然杀伤功能抑制相关联,可能导致HBV感染后高病毒复制能力和不良预后。展开更多
BACKGROUND: Hepatitis B virus (HBV) is a hepatotropic, noncytopathic, DNA virus which can cause acute and chronic infection. Viral persistence is associated with a weak or absent specific immune responses to HBV, part...BACKGROUND: Hepatitis B virus (HBV) is a hepatotropic, noncytopathic, DNA virus which can cause acute and chronic infection. Viral persistence is associated with a weak or absent specific immune responses to HBV, particularly the cellular immune response. Dendritic cells (DCs) are professional antigen-presenting cells with a unique T cell stimulatory aptitude that play a crucial role in the instruction of adaptive immune responses upon infection. An impaired function of DCs was suggested by recent studies to account for the T and B cell hyporesponsiveness in chronic HBV infection. This review summarizes recent insights into the recognition of HBV antigens by DCs. DATA SOURCES: Studies were identified by searching MEDLINE and/or PubMed for articles using the key words 'hepatitis B virus (HBV)', 'dendritic cells', 'C-type lectins', 'mannose receptor', 'toll-like receptor', and 'dendritic cell-specific intercellular-adhesion-molecule-3 grabbing nonintegrin (DC-SIGN)' up to December 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: DCs play an important role in the progress of hepatitis B, especially in the recognition of HBV. There are three main ways of recognition of HBV antigens by DCs. First, HBV DNA can be recognized by DCs through toll-like receptor 9 (TLR9) which activates the NF-kappa B signal pathway and p38 MAPK to up-regulate the expression of interferon (IFN) regulatory factor 7 (IRF-7) in a manner independent of type I IFN signaling, resulting in secretion of type I IFN and inflammatory cytokines, and induction of DC maturation and the adaptive immune response. Second, HBc/HBeAg cannot be recognized by DCs, but DNA or ssRNA encapsulated within HBcAg can be internalized by DCs through TLRs. Third, HBsAg can be internalized by DCs through the mannose receptor, which lacks the ability to induce DC maturation without the assistance of DC-SIGN. Meanwhile, there is some cross-talk among the three mechanisms, which induces an effective anti-viral response or HBV persistence. CONCLUSIONS: On the basis of these recognition processes, methods have been used to enhance the efficacy of DC-based vaccine against HBV and have been useful in the clinical application of HBV vaccine therapy. But the interactions between HBV antigens/HBV DNA and DCs are not clear, and cross-talk between TLRs and various ligands makes HBV antigen recognition by DCs more complicated. More efforts should be made to define the mechanisms and develop effective vaccines and therapies. (Hepatobiliary Pancreat Dis Int 2010; 9:584-592)展开更多
The pre S1 protein of hepatitis B virus(HBV)has been shown to bind to the hepatocytes.However,the hepatocyte receptor for HBV binding has not been cloned yet.The pre S sequence of HBV was inserted into a matnmalian ex...The pre S1 protein of hepatitis B virus(HBV)has been shown to bind to the hepatocytes.However,the hepatocyte receptor for HBV binding has not been cloned yet.The pre S sequence of HBV was inserted into a matnmalian expression vector, Aptag-1,to produce a Alkaline Phusphatase fusion proteins that could be easily and sensitively traced.Efficient expression was achieved in NIH 3T3 cells.This fusion proteins can be used to screen hepatocyte cDNA expression library for the cloning of HBV receptor in hepatocytes.展开更多
文摘目的探讨杀伤细胞免疫球蛋白(KIR)及其配体人类白细胞抗原(HLA)基因的遗传多态性在发生乙肝病毒(HBV)相关性肝癌中的可能作用。方法回顾性分析56例HBV相关性HCC患者与503例健康志愿者的KIR和HLA基因型,探讨KIR基因型、KIR组合型以及KIR-HLA组合型与发生HBV相关性肝癌的相关性。结果比较分析发现,HCC组和对照组KIR基因频率之间的差异无统计学意义(P>0.05)。KIR与其配体HLA-Ⅰ的比较分析中发现,HCC组Bw4频率显著低于对照组(HCC vs control=53.6%vs 66.7%,P=0.05); HCC组2DL2/3+HLA-C1与3DL1+HLA-B Bw4通路的频率显著低于对照组(HCC vs control=67.8%vs 96.0%,P=0.00&HCC vs control=50.0%vs 64.2%,P=0.042)。对KIR基因与HBV-DNA载量关系的调查发现,高载量组中2DS5基因频率均显著高于中载量组和低载量组(High vs Middle=55.6%vs 14.3%,P=0.014&High vs Low 55.6%vs 19.2%,P=0.025)。结论 HCC组中表达KIR-AB3组合型、减少2DL2/3+HLA-C1与3DL1+HLA-B Bw4通路和表达KIR2DS5与NK细胞天然杀伤功能抑制相关联,可能导致HBV感染后高病毒复制能力和不良预后。
基金supported by grants from the Major National Science&Technology Projects for Infectious Diseases(2009ZX10004-309,2008ZX10002-007)the Fundamental Research Funds for the Central Universities(2009QNA7033)the Science and Technology Department Foundation of Zhejiang Province(2010R10061)
文摘BACKGROUND: Hepatitis B virus (HBV) is a hepatotropic, noncytopathic, DNA virus which can cause acute and chronic infection. Viral persistence is associated with a weak or absent specific immune responses to HBV, particularly the cellular immune response. Dendritic cells (DCs) are professional antigen-presenting cells with a unique T cell stimulatory aptitude that play a crucial role in the instruction of adaptive immune responses upon infection. An impaired function of DCs was suggested by recent studies to account for the T and B cell hyporesponsiveness in chronic HBV infection. This review summarizes recent insights into the recognition of HBV antigens by DCs. DATA SOURCES: Studies were identified by searching MEDLINE and/or PubMed for articles using the key words 'hepatitis B virus (HBV)', 'dendritic cells', 'C-type lectins', 'mannose receptor', 'toll-like receptor', and 'dendritic cell-specific intercellular-adhesion-molecule-3 grabbing nonintegrin (DC-SIGN)' up to December 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: DCs play an important role in the progress of hepatitis B, especially in the recognition of HBV. There are three main ways of recognition of HBV antigens by DCs. First, HBV DNA can be recognized by DCs through toll-like receptor 9 (TLR9) which activates the NF-kappa B signal pathway and p38 MAPK to up-regulate the expression of interferon (IFN) regulatory factor 7 (IRF-7) in a manner independent of type I IFN signaling, resulting in secretion of type I IFN and inflammatory cytokines, and induction of DC maturation and the adaptive immune response. Second, HBc/HBeAg cannot be recognized by DCs, but DNA or ssRNA encapsulated within HBcAg can be internalized by DCs through TLRs. Third, HBsAg can be internalized by DCs through the mannose receptor, which lacks the ability to induce DC maturation without the assistance of DC-SIGN. Meanwhile, there is some cross-talk among the three mechanisms, which induces an effective anti-viral response or HBV persistence. CONCLUSIONS: On the basis of these recognition processes, methods have been used to enhance the efficacy of DC-based vaccine against HBV and have been useful in the clinical application of HBV vaccine therapy. But the interactions between HBV antigens/HBV DNA and DCs are not clear, and cross-talk between TLRs and various ligands makes HBV antigen recognition by DCs more complicated. More efforts should be made to define the mechanisms and develop effective vaccines and therapies. (Hepatobiliary Pancreat Dis Int 2010; 9:584-592)
文摘The pre S1 protein of hepatitis B virus(HBV)has been shown to bind to the hepatocytes.However,the hepatocyte receptor for HBV binding has not been cloned yet.The pre S sequence of HBV was inserted into a matnmalian expression vector, Aptag-1,to produce a Alkaline Phusphatase fusion proteins that could be easily and sensitively traced.Efficient expression was achieved in NIH 3T3 cells.This fusion proteins can be used to screen hepatocyte cDNA expression library for the cloning of HBV receptor in hepatocytes.
