Version 1
: Received: 4 December 2021 / Approved: 8 December 2021 / Online: 8 December 2021 (12:06:52 CET)
How to cite:
Kim, J.C.; Lee, H.Y.; Lee, A.R.; Dezhbord, M.; Lee, D.R.; Kim, S.H.; Won, J.; Park, S.; Kim, N.Y.; Shin, J.J.; Kim, S.G.; Kim, Y.S.; Yoo, J.; Kim, K. Identification and Characterization of Besifovir-resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient. Preprints2021, 2021120122. https://doi.org/10.20944/preprints202112.0122.v1
Kim, J.C.; Lee, H.Y.; Lee, A.R.; Dezhbord, M.; Lee, D.R.; Kim, S.H.; Won, J.; Park, S.; Kim, N.Y.; Shin, J.J.; Kim, S.G.; Kim, Y.S.; Yoo, J.; Kim, K. Identification and Characterization of Besifovir-resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient. Preprints 2021, 2021120122. https://doi.org/10.20944/preprints202112.0122.v1
Kim, J.C.; Lee, H.Y.; Lee, A.R.; Dezhbord, M.; Lee, D.R.; Kim, S.H.; Won, J.; Park, S.; Kim, N.Y.; Shin, J.J.; Kim, S.G.; Kim, Y.S.; Yoo, J.; Kim, K. Identification and Characterization of Besifovir-resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient. Preprints2021, 2021120122. https://doi.org/10.20944/preprints202112.0122.v1
APA Style
Kim, J.C., Lee, H.Y., Lee, A.R., Dezhbord, M., Lee, D.R., Kim, S.H., Won, J., Park, S., Kim, N.Y., Shin, J.J., Kim, S.G., Kim, Y.S., Yoo, J., & Kim, K. (2021). <strong>Identification and Characterization of Besifovir-resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient</strong>. Preprints. https://doi.org/10.20944/preprints202112.0122.v1
Chicago/Turabian Style
Kim, J.C., Jeong-Ju Yoo and Kyun-Hwan Kim. 2021 "<strong>Identification and Characterization of Besifovir-resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient</strong>" Preprints. https://doi.org/10.20944/preprints202112.0122.v1
Abstract
Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.
Keywords
hepatitis B virus; besifovir dipivoxil maleate (BSV); nucleos(t)ide analog; drug resistance; reverse transcription
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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