Identification of Novel A2/C2 Inter-Genotype Recombinants of Hepatitis B Virus from a Korean Chronic Patient Co-Infected with Both Genotype A2 and C2.

So-Young Lee,Seung-Hee Lee,Bum-Joon Kim,Yoon-Hoh Kook,Kijeong Kim,Ji-Eun Kim,Hong Kim

doi:10.3390/ijms18040737

So-Young Lee, Seung-Hee Lee + Show 5 more

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https://doi.org/10.3390/ijms18040737

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Abstract

Nearly all cases of Hepatitis B virus (HBV) infections in South Korea have the C2 genotype. Here, we have identified a chronically infected patient who was co-infected with HBV of both the A2 and C2 genotypes by screening 135 Korean chronically infected patients using direct sequencing protocols targeting the 1032-bp polymerase reverse transcriptase (RT) region. Further polymerase chain reaction (PCR)-cloning analysis (22 clones) of the RT showed that this patient had genotype C2 (12 clones), genotype A2 (six clones) and A2/C2 inter-genotype HBV recombinants (four clones). BootScan analysis showed that three of the four recombinants have different types of recombination breakpoints in both the RT and overlapping hepatitis B surface antigen (HBsAg) region. Given the significance of HBsAg as a diagnostic or vaccination target against HBV infection, clinical implications of these identified recombinants should be studied in the future. To our knowledge, this is the first report on A2/C2 inter-genotype HBV recombinants.

Highlights

Hepatitis B virus (HBV) is considered a high-risk factor for chronic liver disease, which can lead to cirrhosis and hepatocellular carcinoma [1,2,3,4]
It has been reported that in addition to more than 350 million people being chronically infected with HBV, the annual number of deaths caused by HBV-related diseases [5], including cirrhosis and hepatocellular carcinoma (HCC), is estimated to be approximately 786,000 worldwide [6]
We report on the first novel HBV recombinants in the polymerase reverse transcriptase (RT) region between genotypes A2 and C2 in a chronically infected patient from South Korea

Summary

Introduction

Hepatitis B virus (HBV) is considered a high-risk factor for chronic liver disease, which can lead to cirrhosis and hepatocellular carcinoma [1,2,3,4]. The genome contains four overlapping open reading frames (ORF) that encode the surface antigen (S), X protein (X), core (C) and polymerase (P), which has reverse transcriptase activity. The reverse transcriptase (RT) of the HBV polymerase consists of 344 amino acids and partially overlaps with the small surface protein (HBsAg). For this reason, mutations in the RT region could result in alterations in the replication capacity, antigenicity, encapsulation, tolerance against antiviral therapy and virulence of HBV [8,9,10]

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