Hepatitis B virus genetic diversity
Hepatitis B virus genetic diversity
复制标题
DOI：
10.1002/jmv.20605
复制
发表时间：
2006-01-01
影响因子：
12.7
通讯作者：
Avellon, Ana
中科院分区：
文献类型：
--
作者：
Echevarria, Jose M.;Avellon, Ana
B型肝炎病毒（HBV）是一种人类DNA病毒，由于其DNA聚合酶的逆转录酶（RT）活性，其通过RNA中间体复制。因此，HBV的突变率高于大多数DNA病毒的突变率。HBV根据基因组测序分为基因型，根据其主要表面糖蛋白HBV表面抗原（HBsAg）的抗原特性分为抗原亚型。已在大多数HBV基因型中鉴定出亚型。在世界各地发现的不同基因型-HBsAg亚型关联定义的HBV组显示出特征性的地理分布，反映了人口的流动和其他流行病学上的重要事件。这些HBV组构成遗传稳定的病毒群体，共享共同的进化史，但在所有这些病毒中观察到源自突变和突变体选择的额外稳定变化。这些病毒亚群被称为HBV变异体，其中一些具有医学和公共卫生相关性。已显示前核心（pre-C）缺陷变体使HBV感染对干扰素治疗的敏感性低得多，并且使用其他抗病毒药物的治疗失败与选择在编码病毒RT活性的基因组区域中显示特定突变的抗性变体相关。由于基因组的RT区与编码HBsAg分子的序列重叠，在某些情况下，药物抗性变体的选择涉及HBsAg变体的间接选择。在慢性HBV携带者中，显示HBsAg变化的病毒变体似乎非常常见;其中一些变体可能在中和抗体应答的压力下出现，导致疫苗耐药性和免疫治疗耐药性。在肝移植受者和HBV携带者母亲所生的婴儿中，经常注意到赋予免疫治疗抗性的突变。此外，这些HBsAg变异体中的一些与用于诊断HBV感染、识别慢性携带者、筛选输血献血和生产治疗性血液制品的HBsAg检测缺乏检测有关。
Hepatitis B virus (HBV) is a human DNA virus, which replicates through an RNA intermediate because of the reverse-transcriptase (RT) activity of its DNA polymerase. As a result, the mutation rate for HBV is higher than the rate observed for most DNA viruses. HBVs are classified into genotypes based on genomic sequencing, and antigenic subtypes based on the antigenic properties of its major surface glycoprotein, the HBV surface antigen (HBsAg). Subgenotypes have been identified within most of the HBV genotypes. The HBV groups defined by the different genotype-HBsAg subtype associations found over the world display characteristic geographical distributions, reflecting the movements of human populations and other epidemiologically significant events. Such HBV groups constitute genetically stable viral populations sharing a common evolutionary history, but additional stable changes, originating from mutation and mutant selection, are observed within all of them. These viral sub-populations are known as the HBV variants, and some of which have medical and public health relevance. Pre-core (pre-C) defective variants have been shown to make HBV infection much less susceptible to interferon treatment, and treatment failures with other antiviral drugs have been associated with selection of resistant variants that display specific mutations in the genome region encoding the viral RT activity. Since the RT region of the genome overlaps the sequence encoding the HBsAg molecule, selection of drug resistant variants involves, in some cases, the indirect selection of HBsAg variants. Viral variants displaying changes in HBsAg seem to be very common among chronic HBV carriers; and some of these variants may emerge under the pressure of the neutralizing antibody response, leading to vaccine resistance and resistance to immunotherapy. Mutations conferring resistance to immunotherapy are noted often among liver transplant recipients and among babies born to HBV-carrier mothers. In addition, some of these HBsAg variants have been associated with lack of detection by HBsAg tests used for the diagnosis of HBV infection, for the identification of chronic carriers, for screening of blood donations for transfusion, and in the manufacture of therapeutic blood products.