在HBV感染患者的HBV整合断裂点中发现不同类型的病毒 - 宿主

StephenW

Mol Med Rep. 2018 Nov 29. doi: 10.3892/mmr.2018.9709. [Epub ahead of print]
Different types of viral‑host junction found in HBV integration breakpoints in HBV‑infected patients.
Ruan P1, Dai X2, Sun J1, He C1, Huang C1, Zhou R1, Cao Z1, Ye L1.
Author information

1
    Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
2
    Department of Breast Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.

Abstract

The present study surveyed the characteristics of hepatitis B virus (HBV) integration in the liver genomes of patients with acute hepatitis B (AHB), carriers of inactive hepatitis B surface antigen (HBsAg), and patients with chronic hepatitis B (CHB) receiving antiviral treatment. 'Short‑read' whole genome sequencing (WGS) with an average of 4,879x coverage for HBV integration was performed in three patients with AHB, two carriers of inactive HBsAg, and 13 patients with CHB receiving antiviral treatment. Conventional polymerase chain reaction and Sanger sequencing were used to verify integration breakpoints supported by at least two paired‑end reads, and viral‑host chimeric transcripts were surveyed simultaneously. HBV integration breakpoints were 100% identified with an average of 138.2±379.9 breakpoints per sample. The numbers of HBV integration breakpoints were positively associated with the sequencing depth coverage numbers and levels of intrahepatic covalently closed circular DNA, respectively (P<0.0001 and P<0.0001). Four types of viral‑host junction in 14 HBV integration breakpoints were detected (two viral junctions mapped in the HBs gene, one in the Precore gene, and others within the HBx gene): Forward simple junction, reverse simple junction, forward and reverse complicated junction, and microhomology were found in many of the junctions. Expression of viral‑human chimeric transcripts was observed in several breakpoints, including the HBs gene. As a result, HBV can integrate into the host gene in the same manner as non‑homologous end joining and microhomology‑mediated end joining with numerous sites, and a close association may exist between HBV integration and patient prognosis. HBx integration may be indispensable for viral‑host chimeric transcription and HBsAg may be produced from integrated DNA.

PMID:
    30535432
DOI:
    10.3892/mmr.2018.9709

StephenW

Mol Med Rep.20188 Nov 29. doi：10.3892 / mmr.2018.9709。 [提前打印]
在HBV感染患者的HBV整合断裂点中发现不同类型的病毒 - 宿主连接。
Ruan P1，Dai X2，Sun J1，He C1，Huang C1，Zhou R1，Cao Z1，Ye L1。
作者信息

1
    武汉大学人民医院消化内科，湖北武汉430060，中国。
2
    湖北医科大学人民医院乳腺外科，湖北十堰442000，中国。

抽象

本研究调查了急性乙型肝炎（AHB），乙型肝炎表面抗原（HBsAg）携带者和接受抗病毒治疗的慢性乙型肝炎（CHB）患者肝脏基因组中乙型肝炎病毒（HBV）整合的特征。治疗。在3例AHB患者，2例非活动性HBsAg携带者和13例接受抗病毒治疗的CHB患者中，进行了“短读”全基因组测序（WGS），平均有4,879倍的HBV整合覆盖率。常规聚合酶链反应和Sanger测序用于验证由至少两个配对末端读数支持的整合断裂点，并且同时测量病毒 - 宿主嵌合转录物。 HBV整合断点100％确定，每个样本平均断裂138.2±379.9。 HBV整合断点的数量分别与肝内共价闭合环状DNA的测序深度覆盖数和水平呈正相关（P <0.0001和P <0.0001）。在14个HBV整合断点中检测到四种类型的病毒 - 宿主连接（HBs基因中定位的两个病毒连接，Precore基因中的一个，以及HBx基因内的其他连接）：前向简单连接，反向简单连接，前向和后向复杂在许多交汇处发现了交汇点和微观同源性。在几个断点中观察到病毒 - 人嵌合转录物的表达，包括HBs基因。结果，HBV可以以与非同源末端连接和微同源介导的末端连接相同的方式整合到宿主基因中，并且可以存在HBV整合与患者预后之间的紧密关联。 HBx整合对于病毒 - 宿主嵌合转录可能是必不可少的，并且HBsAg可以由整合的DNA产生。

结论：
    30535432
DOI：
    10.3892 / mmr.2018.9709