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Cited 3 time in webofscience Cited 3 time in scopus
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Distinctive HBV Replication Capacity and Susceptibility to Tenofovir Induced by a Polymerase Point Mutation in Hepatoma Cell Lines and Primary Human Hepatocyteshepatitis B virus; tenofovir disoproxil fumarate (TDF); reverse transcription; nucleos(t)ide analog; drug resistance

Other Titles
hepatitis B virus; tenofovir disoproxil fumarate (TDF); reverse transcription; nucleos(t)ide analog; drug resistance
Authors
Lee, Ah RamCho, Ju-YeonKim, Jong ChulDezhbord, MehrangizChoo, Soo YeunAhn, Chang HyunKim, Na YeonShin, Jae JinPark, SoreePark, Eun-SookWon, JuheeKim, Dong-SikLee, Jeong-HoonKim, Kyun-Hwan
Issue Date
Feb-2021
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Keywords
hepatitis B virus; tenofovir disoproxil fumarate (TDF); reverse transcription; nucleos(t)ide analog; drug resistance
Citation
International Journal of Molecular Sciences, v.22, no.4
Indexed
SCIE
SCOPUS
Journal Title
International Journal of Molecular Sciences
Volume
22
Number
4
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/52111
DOI
10.3390/ijms22041606
ISSN
1661-6596
Abstract
Tenofovir disoproxil fumarate (TDF) has been regarded as the most potent drug for treating patients with chronic hepatitis B (CHB). However recently, viral mutations associated with tenofovir have been reported. Here, we found a CHB patient with suboptimal response after more than 4 years of TDF treatment. Clonal analysis of hepatitis B virus (HBV) isolated from sequential sera of this patient identified the seven previously reported TDF-resistant mutations (CYELMVI). Interestingly, a threonine to alanine mutation at the 301 amino acid position of the reverse-transcriptase (RT) domain, (rtT301A), was commonly accompanied with CYELMVI at a high rate (72.7%). Since the rtT301A mutation has not been reported yet, we investigated the role of this naturally occurring mutation on the viral replication and susceptibility to tenofovir in various liver cells (hepatoma cells as well as primary human hepatocytes). A cell-based phenotypic assay revealed that the rtT301A mutation dramatically impaired the replication ability with meaningful reduction in sensitivity to tenofovir in hepatoma cell lines. However, attenuated viral replication by the rtT301A mutation was significantly restored in primary human hepatocytes (PHHs). Our findings suggest that the replication capability and drug sensitivity of HBV is different between hepatoma cell lines and PHHs. Therefore, our study emphasizes that validation studies should be performed not only in the liver cancer cell lines but also in the PHHs to understand the exact viral fitness under antiviral pressure in patients.
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2. Clinical Science > Department of Hepato-Biliary-Pancreatic Surgery > 1. Journal Articles

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Kim, Dong-Sik
Anam Hospital (Department of Hepato-Biliary-Pancreatic Surgery, Anam Hospital)
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