APASL2016:差分乙型肝炎病毒宿主和病毒的决定因素 基因型之间

StephenW

O-109
Host and viral determinants for differential hepatitis B virus
clearance between genotypes
Keigo Kawashima1, Masanori Isogawa1, Susumu Tsutsumi1,
Shuko Murakami1, Satoru Saito2, Atsushi Nakajima2, Yasuhito
Tanaka1
1Department of Virology and Liver Unit, Nagoya City University
Graduate School of Medical Science, Nagoya, Japan; 2Department of
Gastroenterology and Hepatology, Yokohama City University School
of Medicine, Yokohama, Japan
Background: Hepatitis B virus (HBV) is categorized into nine
genotypes (A–H, J), and the clinical characteristics differ among
genotypes. Very little is known about the immunological basis for
such difference.
Methods: To examine whether differential HBV clearance rate
between genotypes is associated with HBV-specific CD8 T cell
responses in the liver, HBV genotype C and D were introduced into
C57BL/6J mice by hydrodynamic injection of plasmids containing a
replication competent 1.24-fold HBV-DNA. Serum HBs antigen
(HBsAg) was monitored on days 1, 4 and 14 after hydrodynamic
injections, and intrahepatic expressions of HBV-DNA, HBV-mRNA,
and HBcAg were examined on days 4 and 14. HBV-specific CD8 T
cell responses in the liver was examined on day 14 to correlate with
the aforementioned viral parameters.
Results: Serum HBsAg as well as intrahepatic HBV-DNA and HBVmRNA
expressions persisted longer in the mice expressing genotype
C than genotype D. The delayed clearance of genotype C was associated
with the weaker intrahepatic CD8 T cells on day 14, and the
lower intrahepatic HBcAg expression on day 4. Interestingly, when its
cognate HBcAg expression was transcomplemented by a plasmid
expressing only HBcAg, the clearance of genotype C was accelerated
in association with robust induction of HBV-specific CD8 T cell
responses.
Conclusions: The rate of HBV clearance could differ between
genotypes. The differential clearance rate is associated with the
HBcAg expression levels that determine the magnitude of HBVspecific
CD8 T cell responses.

StephenW

O型109
差分乙型肝炎病毒宿主和病毒的决定因素
基因型之间的间隙
吾Kawashima1，正德矶川1，进堤1，
修子村上1，悟Saito2，淳Nakajima2，保仁
Tanaka1
和病毒学教研室肝单位，名古屋市立大学
医学科学，名古屋，日本的研究生院;教研室
胃肠病学和肝病，横滨市立大学学院
医药，横滨，日本
背景：乙型肝炎病毒（HBV）被分类为九个
基因型（A-H，J），临床特点不同而有差异
基因型。非常知之甚少的免疫学基础
这样的差异。
方法：检查是否差HBV清除率
基因型之间与HBV特异性CD8 T细胞的相关联
在肝脏中的反应，HBV基因型C和D被引入到
C57BL / 6J小鼠含有质粒注射水动力
复制能力的1.24倍HBV-DNA。血清HBs抗原
（HBsAg）的被后流体力学天1,4和14监测
注射剂，和HBV-DNA，HBV-mRNA的肝内表达式
和核心抗原检查天4和HBV特异性14 CD8 + T
在肝细胞的反应进行了检查在第14天与关联
上述病毒的参数。
结果：血清HBsAg以及肝内HBV-DNA和HBVmRNA
表达式的小鼠持续更长的表达基因型
温度比基因型D.延迟C基因型的清除率相关
与第14天的较弱的肝内CD8 T细胞，并且
第4天有趣的是较低的肝内HBcAg的表达，当其
同源HBcAg的表达，质粒transcomplemented
只表达的HBcAg，C基因型的通关速度加快
在乙型肝炎病毒特异性CD8 T细胞的稳健的感应关联
响应。
结论：乙肝病毒清除率可能会有所不同
基因型。差分清除率是与相关联的
HBcAg的表达水平决定HBVspecific的幅度
的CD8 T细胞应答。