[肝胆速递] 乙肝表面抗原监测和慢性肝炎治疗

StephenW

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谢谢。什么原因没有人研究乙型肝炎病毒的受体?即使在​​鸭乙型肝炎模型?

bigben446

StephenW 发表于 2011-5-30 14:05
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谢谢。什么原因没有人研究乙型肝炎病毒的受体?即使在​​鸭乙型肝炎模型? ...

鸭乙肝病毒是双受体，一个是Carboxypeptidase D，一个是Glycine decarboxylase，前面一个很确定，但是鸭乙肝病毒和乙肝病毒还不同。

研究乙肝病毒受困的根本原因是缺乏好的细胞感染模型，前几年才刚刚发现第一株可被乙肝病毒感染的细胞株HepaRG，但是感染效率仍然低下，没有好的细胞感染模型自然很难研究早期感染机制受体什么的。幸好乙肝病毒的细胞复制模型很早就发现了，所以用来研究核苷类似物还是很方便的。

StephenW

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鸭乙肝病毒是双受体，一个是Carboxypeptidase D，一个是Glycine decarboxylase，前面一个很确定，但是鸭乙肝病毒和乙肝病毒还不同。
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因此，REP 9AC(as surface exit/entry inhibitor)在鸭模型试验，结果可能不被应用于人类?

bigben446

这个里面涉及几个概念，可以用这几个关键词搜索到更多的文章。


Superinfection
Superinfection  exclusion  is  a  phenomenon  whereby  a  cell
infected with a virus is resistant to superinfection by the same
virus. Superinfection exclusion is observed during infections by
a broad range of viruses, including HIV，vesicular stomatitis virus (VSV), vaccinia virus, and alphavirus.
目前认为HBV和DHBV都不例外，病毒方面是通过大S蛋白进行的。

Regeneration（或者Hepatocyte Turnover）
肝细胞分裂很快，不过关于肝细胞分裂对乙肝感染的影响讨论倒是和乙肝病毒清除机制相关的。


相关讨论：
There is some evidence to
suggest that superinfection exclusion occurs in hepadnavirus
infections  as  well.  When  liver  transplant  and  nontransplant
patients with chronic HBV infections were treated with lami-
vudine, differences in the patterns of development of lamivu-
dine resistance could be seen. The average duration of lami-
vudine monotherapy before resistant HBV variants emerged
was  longer  in  nontransplant  patients  than  in  transplant  pa-
tients, 562 days versus 371 days, respectively (11). In addition,
the  rates  of  resistance  appeared  to  be  higher  in  transplant
patients than in nontransplant patients (8, 16, 23). These re-
sults suggest that lamivudine-resistant HBV establishes an in-
fection more readily in an uninfected liver than in an HBV-
infected liver.
Recent  studies  with  the  DHBV  animal  model  have  also
suggested that superinfection exclusion occurs in avian hepad-
navirus infections. Studies of viral kinetics in ducks have shown
that enrichment of wild-type DHBV over replication-defective
mutants is rapid during the initial spread of infection. There-
after, the enrichment rate is slower and appears to be depen-
dent on the generation of new, uninfected hepatocytes (40, 41).
In a similar study, the emergence of wild-type DHBV in com-
petition with either cytopathic or noncytopathic DHBV was
found to be dependent on cell death caused by the cytopathic
virus, because the wild-type virus did not emerge in competi-
tion studies with the noncytopathic variant (18).

bigben446

StephenW 发表于 2011-5-30 14:18
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鸭乙肝病毒是双受体，一个是Carboxypeptidase D，一个是Glycine decarboxylase，前 ...

印象中REP 9AC好像是个广谱的抑制剂（除了乙肝还有其他病毒亦有效），具体内容我不知，没看他的资料。

temp

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还有一些文章说到核甘治疗过程中病毒变异造成失代偿等等，可见免疫对变异病毒的识别和清除非常迅猛。

temp

bigben446 发表于 2011-5-30 13:19
耐药前后的P蛋白氨基酸变化，S蛋白氨基酸变化还是什么？
已经有好多行业内专家写的综述啦，到pubmed上搜 ...

我猜你是说的是血液中表面抗原在耐药前后的定量的变化
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没错，就是指两对半指标，这个更直观一些。

StephenW

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印象中REP 9AC好像是个广谱的抑制剂（除了乙肝还有其他病毒亦有效)
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我的印象REP 9AC不是抑制剂, 更像Myrcludex.

请问肝细胞从(liver cells from)成人干细胞(adult stem cells)会帮助受体(receptor)的研究？

bigben446

StephenW 发表于 2011-5-30 15:10
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印象中REP 9AC好像是个广谱的抑制剂（除了乙肝还有其他病毒亦有效)

Our drug is a first-in-class surface antigen release inhibitor. It prevents the release of a viral protein called surface antigen from infected liver cells (hepatocytes). Mounting evidence is now showing that surface antigen acts to suppress the immune response to HBV infection and may allow the infection to be chronically maintained in the liver. The administration of our drug to animals or humans results in a rapid reduction and elimination of surface antigen in the blood. This reduction is associated with a restoration of the immune system’s capability to fight the infection as demonstrated by the development of antibodies against surface antigen. In other words, the removal of surface antigen from the blood gives patients the ability to successfully fight their infection on their own. In addition, because of its mechanism of action, the development of resistance to our drug is very unlikely.

http://www.replicor.com/debut_anglais2.htm

原代肝细胞可以也用的很久了，但是远远没有细胞系来得方便。干细胞什么的，还没听到应用于乙肝研究。理论上可以，到实践是另外一回事，到大规模实验室应用又是另外一回事，到临床实践更是另外一回事，少部分很快，但是绝大部分要很多时间。

StephenW

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细胞系 means cell line (liver cells that can divide and survive in a dish)?