基于cell-in-cell结构介导HBV传播新机制的研究

The lack of in vitro model hinders mechanistic study of HBV infection in hepatocytes. The establishment of HepG2hNTCP HBV infection system has revolutionized the field of HBV research. Recently, there is a growing interests in the cell-in-cell structure as an important pathway for viral infection. The applicant had been established this new method, which confirmed HCV could infect hepatocytes by cell-in-cell structure at University of Birmingham. Cell-in-cell infection means viruses could transmission infection from carried or infected cells to target cells. There are evidence showing PBMCs being able to be infected and carried HBV in infected patients. Here we hypothesize that the cell-in-cell structure can be an alternative route for HBV infected infection. The combination of the applicant’s study experience, HepG2hNTCP cell lines were obtained and the technology of cell-in-cell research was acquired, we have enough reasons to carry out similar studies. The aim of this study is to use primary lymphocytes or cell lines and liver tissue to explore the mechanism of HBV infection hepatocytes. Our results will remedy some defects of HBV infection pathways and propose some new valuable clues for clinical treat of HBV inhibition.

HBV体外感染理想模型的缺失阻碍HBV感染肝细胞机制研究，但HBV感染模型HepG2hNTCP建立，有望破解HBV感染的具体机制。申请者在伯明翰大学已经建立由cell-in-cell途径证实HCV可以通过此种新型方法感染肝细胞，这种途径已经成为多种病毒感染方式而成为研究热点。cell-in-cell感染方式为一种附带或感染病毒的细胞进入目标细胞内，通过一系列的介导途径将病毒感染至目标细胞。加之体内PBMC感染或携带HBV证据持续报道，提出HBV可能经由cell-in-cell结构感染肝细胞新型方式的合理假设。其中HepG2hNTCP细胞系的获得和cell-in-cell研究技术的熟练开展是关键，以各种细胞系和原代淋巴细胞及肝脏组织开展HBV新型感染研究，探讨HBV的cell-in-cell感染和影响机制，弥补HBV感染方式的缺陷，为临床阻断和治疗HBV感染肝细胞的新机理提出有价值的新线索。