乙型肝炎病毒中的新型遗传重排：复杂结构变异和结构变异多态性。

Novel Genetic Rearrangements in Hepatitis B Virus: Complex Structural Variations and Structural Variation Polymorphisms.

机构信息

Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.

出版信息

Viruses. 2021 Mar 12;13(3):473. doi: 10.3390/v13030473.

DOI:10.3390/v13030473

PMID:33809245

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8000817/

Abstract

Chronic hepatitis B virus (HBV) causes serious clinical problems, such as liver cirrhosis and hepatocellular carcinoma. Current antiviral treatments suppress HBV; however, the clinical cure rate remains low. Basic research on HBV is indispensable to eradicate and cure HBV. Genetic alterations are defined by nucleotide substitutions and canonical forms of structural variations (SVs), such as insertion, deletion and duplication. Additionally, genetic changes inconsistent with the canonical forms have been reported, and these have been termed complex SVs. Detailed analyses of HBV using bioinformatical applications have detected complex SVs in HBV genomes. Sequence gaps and low sequence similarity have been observed in the region containing complex SVs. Additionally, insertional motif sequences have been observed in HBV strains with complex SVs. Following the analyses of complex SVs in the HBV genome, the role of SVs in the genetic diversity of orthohepadnavirus has been investigated. SV polymorphisms have been detected in comparisons of several species of orthohepadnaviruses. As mentioned, complex SVs are composed of multiple SVs. On the contrary, SV polymorphisms are observed as insertions of different SVs. Up to a certain point, nucleotide substitutions cause genetic differences. However, at some point, the nucleotide sequences are split into several particular patterns. These SVs have been observed as polymorphic changes. Different species of orthohepadnaviruses possess SVs which are unique and specific to a certain host of the virus. Studies have shown that SVs play an important role in the HBV genome. Further studies are required to elucidate their virologic and clinical roles.

摘要

慢性乙型肝炎病毒 (HBV) 可引起严重的临床问题，如肝硬化和肝细胞癌。目前的抗病毒治疗可抑制 HBV；然而，临床治愈率仍然较低。HBV 的基础研究对于根除和治愈 HBV 是必不可少的。遗传改变定义为核苷酸取代和结构变异 (SV) 的典型形式，如插入、缺失和重复。此外，还报道了不符合典型形式的遗传变化，这些变化被称为复杂 SV。使用生物信息学应用程序对 HBV 进行详细分析，在 HBV 基因组中检测到了复杂 SV。在包含复杂 SV 的区域观察到序列缺口和低序列相似性。此外，在具有复杂 SV 的 HBV 株中观察到插入模序序列。在分析 HBV 基因组中的复杂 SV 后，研究了 SV 在正嗜肝 DNA 病毒遗传多样性中的作用。在比较几种正嗜肝 DNA 病毒时，检测到了 SV 多态性。如前所述，复杂 SV 由多个 SV 组成。相反，SV 多态性被观察为不同 SV 的插入。在一定程度上，核苷酸取代会导致遗传差异。然而，在某些时候，核苷酸序列会分成几个特定的模式。这些 SV 被观察为多态性变化。不同种的正嗜肝 DNA 病毒具有独特的和特定于病毒宿主的 SV。研究表明，SV 在 HBV 基因组中发挥着重要作用。需要进一步研究来阐明它们的病毒学和临床作用。