a Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine , University of Calgary , Calgary , Canada.
b Department of Microbiology, Immunology and Infectious Diseases , Cumming School of Medicine, University of Calgary , Calgary , Canada.
Biotechnol Genet Eng Rev. 2018 Apr;34(1):139-151. doi: 10.1080/02648725.2018.1474324. Epub 2018 May 22.
The hepatitis B virus (HBV) is predominantly a hepatotropic virus but also infects cells of the lymphatic system. HBV genomes (DNA, messenger (m)RNA, covalently closed circular (ccc) DNA) and proteins have been found in extrahepatic sites such as peripheral blood mononuclear cells (PBMC), lymph nodes, spleen, bone marrow and cerebrospinal fluid. HBV entry into hepatocytes occurs by binding of the HBV preS1 surface protein to its specific receptor, the bile acid transporter, sodium taurocholate co-transporting polypeptide (NTCP). Although the mechanism of HBV entry into lymphatic cells is unknown, the pre S1 encoded surface protein is thought to be involved. Extrahepatic HBV infection has been studied in both chronic HBV (CHB) and in occult HBV infection (OBI). Studies have shown that HBV genomes are present in different PBMC subsets from chronically infected carriers. Unique HBV variants have been found in PBMC compared to plasma or liver in both nucleos(t)ide analogue (NA) treated and untreated CHB carriers, suggesting replication and compartment specific evolution of HBV. In HBV coinfection, HBV genomes were found in PBMC from hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis delta virus (HDV) co-infected individuals. Moreover, during pregnancy, the trans placental passage of HBV infected PBMC from highly viremic mothers to infants is one of the postulated means of vertical transmission of HBV. Taken together, HBV infection in extrahepatic sites (i.e., PBMC) is implicated in multiple facets of HBV pathogenesis such as persistence, viral evolution and vertical transmission.
乙型肝炎病毒 (HBV) 主要是一种嗜肝病毒，但也感染淋巴系统的细胞。HBV 基因组（DNA、信使 (m)RNA、共价闭合环状 (ccc) DNA）和蛋白质已在肝外部位如外周血单核细胞 (PBMC)、淋巴结、脾脏、骨髓和脑脊液中发现。HBV 进入肝细胞是通过 HBV preS1 表面蛋白与其特异性受体胆汁酸转运蛋白、牛磺胆酸钠共转运多肽 (NTCP) 结合实现的。虽然 HBV 进入淋巴细胞的机制尚不清楚，但认为 pre S1 编码的表面蛋白参与其中。慢性乙型肝炎 (CHB) 和隐匿性乙型肝炎感染 (OBI) 都对肝外 HBV 感染进行了研究。研究表明，HBV 基因组存在于慢性感染携带者的不同 PBMC 亚群中。与未接受核苷（酸）类似物 (NA) 治疗和治疗的 CHB 携带者的血浆或肝脏相比，在 PBMC 中发现了独特的 HBV 变体，这表明 HBV 在复制和特定部位发生了进化。在 HBV 合并感染中，在丙型肝炎病毒 (HCV)、人类免疫缺陷病毒 (HIV) 和乙型肝炎 delta 病毒 (HDV) 合并感染个体的 PBMC 中发现了 HBV 基因组。此外，在怀孕期间，来自高病毒血症母亲的 HBV 感染 PBMC 通过胎盘向婴儿的转移是 HBV 垂直传播的一种假设方式。综上所述，肝外部位（即 PBMC）的 HBV 感染与 HBV 持续存在、病毒进化和垂直传播等多个方面的发病机制有关。
