乙型肝炎病毒基因组多样性的演变及其临床影响

StephenW

The evolution and clinical impact of hepatitis B virus genome diversity

    Peter A. Revill, Thomas Tu, Hans J. Netter, Lilly K. W. Yuen, Stephen A. Locarnini & Margaret Littlejohn

Nature Reviews Gastroenterology & Hepatology volume 17, pages618–634(2020)Cite this article

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Abstract

The global burden of hepatitis B virus (HBV) is enormous, with 257 million persons chronically infected, resulting in more than 880,000 deaths per year worldwide. HBV exists as nine different genotypes, which differ in disease progression, natural history and response to therapy. HBV is an ancient virus, with the latest reports greatly expanding the host range of the Hepadnaviridae (to include fish and reptiles) and casting new light on the origins and evolution of this viral family. Although there is an effective preventive vaccine, there is no cure for chronic hepatitis B, largely owing to the persistence of a viral minichromosome that is not targeted by current therapies. HBV persistence is also facilitated through aberrant host immune responses, possibly due to the diverse intra-host viral populations that can respond to host-mounted and therapeutic selection pressures. This Review summarizes current knowledge on the influence of HBV diversity on disease progression and treatment response and the potential effect on new HBV therapies in the pipeline. The mechanisms by which HBV diversity can occur both within the individual host and at a population level are also discussed.
Key points

    Hepatitis B virus (HBV) is an ancient virus with deep ancestry in the animal kingdom.

    HBV seems to undergo very little long-term mutational variation despite multiple host–virus factors driving short-term viral variations.

    Viral diversity is generated by features of the unique replication cycle of HBV as well as by cellular host factors.

    A possible bottleneck in the establishment of new viral variants could be the limited number of HBV-susceptible hepatocytes in the chronically infected liver.

    HBV viral diversity contributes to variations in natural history, disease progression and treatment response in those with chronic infection.

    Viral diversity must be considered in the development of new therapeutic regimens.

StephenW

乙型肝炎病毒基因组多样性的演变及其临床影响

    Peter A.Revill，Thomas Tu，Hans J.Netter，Lilly K.W.Yen，Stephen A.Locarnini和Margaret Littlejohn

自然评论，胃肠病和肝病，第17卷，第618–634页（2020年）

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抽象

乙型肝炎病毒（HBV）的全球负担是巨大的，有2.57亿人被慢性感染，导致全世界每年有880,000多人死亡。 HBV以九种不同的基因型存在，它们在疾病进展，自然病史和对治疗的反应方面均不同。乙肝病毒是一种古老的病毒，最新报道极大地扩展了嗜肝病毒科（包括鱼类和爬行动物）的宿主范围，并为该病毒家族的起源和进化提供了新的思路。尽管有一种有效的预防性疫苗，但仍不能治愈慢性乙型肝炎，这在很大程度上归因于目前治疗方法未靶向的病毒微型染色体的持续存在。 HBV持久性也可通过异常的宿主免疫反应来促进，这可能是由于宿主内不同的病毒种群可以对宿主的选择压力和治疗选择压力做出反应。这篇综述总结了有关HBV多样性对疾病进展和治疗反应的影响的最新知识，以及对管线中新HBV疗法的潜在影响。还讨论了HBV多样性可在个体宿主内和人群中发生的机制。
关键点

    乙型肝炎病毒（HBV）是一种古老的病毒，在动物界具有深厚的血统。

    尽管有多种宿主病毒因素驱动短期病毒变异，但HBV似乎很少发生长期变异变异。

    病毒多样性是由HBV独特复制周期的特征以及细胞宿主因子产生的。

    建立新的病毒变体的可能瓶颈可能是慢性感染肝脏中的HBV易感性肝细胞数量有限。

    HBV病毒多样性导致慢性感染者的自然史，疾病进展和治疗反应发生变化。

    在开发新的治疗方案时必须考虑病毒多样性。