Characterization of hepatitis B virus with complex structural variations

Kei Fujiwara,Etsuko Iio,Kentaro Matsuura,Shunsuke Nojiri,Kayoko Matsunami

doi:10.1186/s12866-018-1350-1

Abstract

BackgroundHepatitis B virus (HBV) infection is one of the most serious public health issues. Recent HBV genetic research has revealed novel genetic rearrangements termed complex structural variations (SVs), which are composed of combinations of SVs such as insertions, deletions, and duplications. An extensive search was made for complex SVs of HBV and their characteristics were analyzed.ResultsFifty-five HBV strains with complex SVs were identified by analyzing genetic sequences of HBV with bioinformatical tools. Along with 15 HBV strains with complex SVs in a previous report, a total of 70 HBV strains harboring complex SVs were analyzed. Complex SVs in the HBV genome were located frequently between nt 1500 and 2000. Insertions were observed in 65/70 (92.9%) of HBV strains with complex SVs. As insertional motif sequences, hepatocyte nuclear factor 1 binding site, a sequence complementary to part of box α in enhancer II, and insertions of unknown origins were observed. The complex SVs were classified into six groups, and combination of insertion and deletion was observed more frequently than other patterns.ConclusionThrough an extensive search of HBV sequences, new strains with complex SVs were identified in this study. Characteristics of HBV with complex SVs were clarified by the analysis of 70 HBV strains harboring complex SVs. Further investigation is required to elucidate its role in pathogenesis of HBV-related liver disease.

Highlights

Hepatitis B virus (HBV) infection is one of the most serious public health issues
257 million people are estimated to be infected with HBV, as diagnosed by hepatitis B surface antigen (HBs-Ag) positivity, and HBV-related liver cirrhosis and hepatocellular carcinoma cause approximately 900,000 deaths annually [1]
PubMed search of HBV strains with complex Structural variation (SV) A search in PubMed for additional HBV strain with complex SVs retrieved 203 abstracts or full text articles, which were manually reviewed

Summary

Introduction

Recent HBV genetic research has revealed novel genetic rearrangements termed complex structural variations (SVs), which are composed of combinations of SVs such as insertions, deletions, and duplications. Hepatitis B virus (HBV) infection causes acute hepatitis and chronic liver disease. 257 million people are estimated to be infected with HBV, as diagnosed by hepatitis B surface antigen (HBs-Ag) positivity, and HBV-related liver cirrhosis and hepatocellular carcinoma cause approximately 900,000 deaths annually [1]. Treatment to cure the infection has not been achieved and patients with chronic hepatitis B require long-term treatment [2]. Treatment to achieve a cure in a short period of time is required. For this purpose, fundamental research leading to further understanding of viral replication and the viral genome structure is very important

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