The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation

PLoS Pathogens
Quanxin LongHaitao Guo

Abstract

Hepadnavirus covalently closed circular (ccc) DNA is the bona fide viral transcription template, which plays a pivotal role in viral infection and persistence. Upon infection, the non-replicative cccDNA is converted from the incoming and de novo synthesized viral genomic relaxed circular (rc) DNA, presumably through employment of the host cell's DNA repair mechanisms in the nucleus. The conversion of rcDNA into cccDNA requires preparation of the extremities at the nick/gap regions of rcDNA for strand ligation. After screening 107 cellular DNA repair genes, we herein report that the cellular DNA ligase (LIG) 1 and 3 play a critical role in cccDNA formation. Ligase inhibitors or functional knock down/out of LIG1/3 significantly reduced cccDNA production in an in vitro cccDNA formation assay, and in cccDNA-producing cells without direct effect on viral core DNA replication. In addition, transcomplementation of LIG1/3 in the corresponding knock-out or knock-down cells was able to restore cccDNA formation. Furthermore, LIG4, a component in non-homologous end joining DNA repair apparatus, was found to be responsible for cccDNA formation from the viral double stranded linear (dsl) DNA, but not rcDNA. In conclusion, we demonstrate that...Continue Reading

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Citations

Jun 22, 2018·PLoS Pathogens·Kouichi KitamuraMasamichi Muramatsu
Mar 29, 2019·Life Science Alliance·Peter Ac WingJane A McKeating
Aug 9, 2019·PLoS Pathogens·Luhua Qiao, Guangxiang George Luo
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Aug 4, 2019·Journal of Virology·Jianming HuAleem Siddiqui
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Sep 19, 2020·Microorganisms·Magda Rybicka, Krzysztof Piotr Bielawski
Oct 21, 2020·PLoS Pathogens·Sheng ShenHaitao Guo
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Sep 24, 2018·Gastroenterology·Jianming HuTakaji Wakita
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Jun 13, 2018·ACS Infectious Diseases·Jin HuJu-Tao Guo
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Sep 30, 2021·Annual Review of Virology·Timothy M BlockJu-Tao Guo
Dec 14, 2021·Cellular and Molecular Gastroenterology and Hepatology·Zaichao XuYuchen Xia

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Datasets Mentioned

BETA
U95551

Methods Mentioned

BETA
gene knock-down
PCR
gene knock-out
transfection
electrophoresis
fluorescence microscopy
dot blotting
dot blot
transfect

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