Pathogenesis of hepatitis B virus infection.
Pathogenesis of hepatitis B virus infection.
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DOI：
10.1016/j.patbio.2009.11.001
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发表时间：
2010-08
影响因子：
--
通讯作者：
Wieland, S. F.
中科院分区：
文献类型：
--
作者：
Chisari, F. V.;Isogawa, M.;Wieland, S. F.
关键词：
适应性免疫应答被认为是负责病毒清除和疾病的发病机制在B型肝炎病毒感染。一般认为，体液抗体应答有助于清除循环病毒颗粒并防止病毒在宿主内传播，而细胞免疫应答则消除受感染的细胞。T细胞对B型肝炎病毒（HBV）的应答在成功清除病毒的急性感染患者中是强有力的、多克隆的和多特异性的，而在慢性感染患者中相对较弱且狭窄地集中，这表明HBV的清除是T细胞依赖性的。细胞毒性T淋巴细胞（CTL）对HBV的致病性和抗病毒潜力已被证明是由一个严重的坏死性肝脏疾病的诱导后，过继转移HBsAg特异性CTL到HBV转基因小鼠。值得注意的是，CTL还通过分泌1型炎性细胞因子从肝脏清除HBV复制中间体，从而限制病毒扩散到未感染的细胞并降低终止感染所需的免疫病理学程度。持续性HBV感染的特征在于弱的适应性免疫应答，这被认为是由于在感染早期低效的CD4+ T细胞致敏以及随后在定量和定性上无效的CD8+ T细胞应答的发展。可能导致病毒持续存在的其他因素是免疫耐受、突变表位失活、T细胞受体拮抗、病毒复制的不完全下调和免疫特权组织的感染。然而，这些途径仅在无效免疫应答的情况下变得明显，因此，这是根本的潜在原因。持续感染的特征是慢性肝细胞损伤、再生、炎症、广泛的DNA损伤和细胞生长控制基因的插入失调，这些共同导致肝硬化和肝细胞癌。
The adaptive immune response is thought to be responsible for viral clearance and disease pathogenesis during hepatitis B virus infection. It is generally acknowledged that the humoral antibody response contributes to the clearance of circulating virus particles and the prevention of viral spread within the host while the cellular immune response eliminates infected cells. The T cell response to the hepatitis B virus (HBV) is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focussed in chronically infected patients, suggesting that clearance of HBV is T cell dependent. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV has been proven by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBsAg specific CTL into HBV transgenic mice. Remarkably, the CTLs also purge HBV replicative intermediates from the liver by secreting type 1 inflammatory cytokines thereby limiting virus spread to uninfected cells and reducing the degree of immunopathology required to terminate the infection. Persistent HBV infection is characterized by a weak adaptive immune response, thought to be due to inefficient CD4+ T cell priming early in the infection and subsequent development of a quantitatively and qualitatively ineffective CD8+ T cell response. Other factors that could contribute to viral persistence are immunological tolerance, mutational epitope inactivation, T cell receptor antagonism, incomplete down-regulation of viral replication and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective immune response which is, therefore, the fundamental underlying cause. Persistent infection is characterized by chronic liver cell injury, regeneration, inflammation, widespread DNA damage, and insertional deregulation of cellular growth control genes which, collectively, lead to cirrhosis of the liver and hepatocellular carcinoma.
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DOI：
10.1073/pnas.88.10.4186
发表时间：
1991-05-01
影响因子：
11.1
作者：
BRUNETTO, MR;GIARIN, MM;BONINO, F
通讯作者：
BONINO, F
影响因子：
158.5
作者：
ERIKSSON, S;CARLSON, J;VELEZ, R
通讯作者：
VELEZ, R
DOI：
10.1073/pnas.88.23.10445
发表时间：
1991-12-01
影响因子：
11.1
作者：
BERTOLETTI, A;FERRARI, C;CHISARI, FV
通讯作者：
CHISARI, FV
影响因子：
3.7
作者：
Bruni, R;D'Ugo, E;Rapicetta, M
通讯作者：
Rapicetta, M
影响因子：
64.5
作者：
CHISARI, FV;KLOPCHIN, K;PALMITER, RD
通讯作者：
PALMITER, RD