Hepatitis B viral replication influences the expression of natural killer cell ligands.
Hepatitis B viral replication influences the expression of natural killer cell ligands.
复制标题
DOI：
10.20524/aog.2016.0036
复制
发表时间：
2016-07
影响因子：
2.2
通讯作者：
Khakoo SI
中科院分区：
文献类型：
--
作者：
Koumbi L;Pollicino T;Raimondo G;Kumar N;Karayiannis P;Khakoo SI
由于免疫介导的慢性肝损伤，每年有100多万人死于乙肝病毒(HBV)。自然杀伤(NK)细胞在肝脏中含量丰富，对乙肝病毒的持续存在起着重要作用。NK细胞毒作用受激活受体和抑制受体信号的控制。乙肝病毒可能通过调节NK受体及其配体来规避宿主的抗病毒免疫。我们研究了病毒复制和HBeAg突变对慢性乙型肝炎(CHB)患者肝脏和细胞培养中NK介体表达的影响。用无质粒法将基本核心启动子和前C区热点突变的乙肝病毒单体导入HepG2细胞。对19例慢性乙型病毒性肝炎患者进行了血清病毒血症和肝脏HBVRNA检测。检测HBVRNA、NKG2D配体、B7H6、DNAX辅助分子-1、凝集素样转录本1(LLT1)、LFA-1和TRAIL在CHB患者和转基因细胞中的表达。总体而言，慢性乙型肝炎患者和细胞系中的高复制可上调所有NK细胞配体，特别是抑制性NK细胞配体LLT1的mRNA表达。除了NKG2D配体MICA外，在血清病毒血症和肝内HBVRNA水平较高的患者中，NKG2D配体MICA显著降低。乙肝病毒复制对NK细胞配体有不同的影响，提示可能通过上调LLT1和下调MICA而逃逸。NK细胞配体上调的总体趋势可以通过减少MICA从而削弱NK监视来抵消。
Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. In general, high HBV replication in CHB patients and cell lines upregulated the mRNA of all NK cell ligands and particularly the inhibitory NK cell ligand, LLT1. The exception was the NKG2D ligand, MICA, that was significantly decreased in patients with high serum viremia and intrahepatic HBV RNA levels. HBV replication has differential effects on NK cell ligands suggesting a potential escape mechanisms through up-regulation of LLT1 and down-regulation of MICA. A general trend towards upregulating NK cell ligands can be counteracted by decreasing MICA and hence weakening NK surveillance.