HBV DNA 整合最初被认为是 HBV 生命周期的非功能性副产品，现在已被认为是 HBV 发病机制和 HDV 持续存在的重要因素。整合的 HBV DNA 源自病毒颗粒中存在的线性基因组 DNA，或由感染后异常加工的松弛环状基因组 DNA 产生，并且可以驱动 HBsAg 和 HBx 的表达。 DNA 整合事件在病毒感染过程中不断积累，范围从早期阶段的百分之几到长期慢性感染后感染细胞的近 100%。 HBV DNA 整合事件主要在 HCC 发展的背景下进行研究，其中它们可以激活已知的癌基因和其他生长促进基因，导致染色体不稳定，并可能导致促进肿瘤生长的表观遗传改变。最近的证据表明，整合 DNA 的 HBsAg 表达可能通过减弱免疫反应而促进 HBV 发病。整合的 DNA 提供了 HDV 复制所需的包膜蛋白来源，因此代表了 HDV 持久性的一种手段。由于整合的 DNA 负责在没有病毒复制的情况下 HBsAg 的持续存在，因此它会影响依赖 HBsAg 作为诊断标记物的 HBV 感染解决的既定标准。整合的 HBV DNA 可用于评估受感染肝细胞的更新，这种更新发生在慢性乙型肝炎的所有阶段，包括历史上称为免疫耐受的感染初始阶段。 HBV DNA 整合也被证明会影响针对病毒 RNA 的新型疗法的开发。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

HBV DNA integration originally recognized as a non-functional byproduct of the HBV life cycle has now been accepted as a significant contributor to HBV pathogenesis and HDV persistence. Integrated HBV DNA is derived from linear genomic DNA present in virus particles or produced from aberrantly processed relaxed circular genomic DNA following an infection, and can drive expression of HBsAg and HBx. DNA integration events accumulate over the course of viral infection ranging from a few percent during early phases to nearly 100 percent of infected cells after prolonged chronic infection. HBV DNA integration events have primarily been investigated in the context of HCC development where they can activate known oncogenes and other growth promoting genes, cause chromosomal instability and presumably epigenetic alterations promoting tumor growth. More recent evidence suggests that HBsAg expression from integrated DNA might contribute to HBV pathogenesis by attenuating the immune response. Integrated DNA provides a source for envelope proteins required for HDV replication and hence represents a means for HDV persistence. Because integrated DNA is responsible for persistence of HBsAg in the absence of viral replication it impacts established criteria for the resolution of HBV infection which relies on HBsAg as a diagnostic marker. Integrated HBV DNA has been useful in assessing the turnover of infected hepatocytes which occurs during all phases of chronic hepatitis B including the initial phase of infection historically termed immune tolerant. HBV DNA integration was also shown to impact the development of novel therapies targeting viral RNAs.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.