Medical virology of hepatitis B: how it began and where we are now.

Medical virology of hepatitis B: how it began and where we are now.
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DOI:
10.1186/1743-422x-10-239
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发表时间:
2013-07-20
期刊:
影响因子:
4.8
通讯作者:
Gerlich WH
Gerlich WH
中科院分区:
医学3区
文献类型:
--
作者:
Gerlich WH

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感染B型肝炎病毒(HBV)可导致急性或慢性肝炎。HBV感染以前更频繁,但今天仍然有2.4亿慢性HBV携带者,大约有2.5亿人。每年有62万人死于晚期后遗症肝硬化或肝细胞癌。B型肝炎在古代就被认为是一种疾病,但其病原体直到最近才被确定。解开这个谜团的第一条线索是50年前巴鲁克·布伦伯格发现了一种名为澳大利亚抗原的神秘血清蛋白。几年后,这被认为是HBV表面抗原(HBsAg)。HBsAg的检测首次允许对潜在感染的献血者进行危险病原体的筛查。诊断临床无症状HBV感染的需要是现代病毒诊断发展的强大驱动力。HBsAg是第一个用高灵敏度放射免疫测定法测定的感染标志物。HBV本身是通过其DNA基因组测定检测的首批病毒之一,抗HBV核心抗原的IgM抗体是通过抗μ捕获测定选择性检测的首批病毒。1978年HBV基因组的克隆和测序为了解病毒生命周期铺平了道路,并允许开发高效的疫苗和药物。今天的B型肝炎疫苗是第一个通过基因技术生产的疫苗。目前仍然存在的问题是无法完全治愈慢性HBV感染,识别隐匿性HBV感染,其潜在的再活化以及HBV疫苗对逃逸突变体和异源HBV基因型的不完全保护。
Infection with hepatitis B virus (HBV) may lead to acute or chronic hepatitis. HBV infections were previously much more frequent but there are still 240 million chronic HBV carriers today and ca. 620,000 die per year from the late sequelae liver cirrhosis or hepatocellular carcinoma. Hepatitis B was recognized as a disease in ancient times, but its etiologic agent was only recently identified. The first clue in unraveling this mystery was the discovery of an enigmatic serum protein named Australia antigen 50 years ago by Baruch Blumberg. Some years later this was recognized to be the HBV surface antigen (HBsAg). Detection of HBsAg allowed for the first time screening of inapparently infected blood donors for a dangerous pathogen. The need to diagnose clinically silent HBV infections was a strong driving force in the development of modern virus diagnostics. HBsAg was the first infection marker to be assayed with a highly sensitive radio immune assay. HBV itself was among the first viruses to be detected by assay of its DNA genome and IgM antibodies against the HBV core antigen were the first to be selectively detected by the anti-μ capture assay. The cloning and sequencing of the HBV genome in 1978 paved the way to understand the viral life cycle, and allowed development of efficient vaccines and drugs. Today’s hepatitis B vaccine was the first vaccine produced by gene technology. Among the problems that still remain today are the inability to achieve a complete cure of chronic HBV infections, the recognition of occult HBV infections, their potential reactivation and the incomplete protection against escape mutants and heterologous HBV genotypes by HBV vaccines.