Asymmetric Modification of Hepatitis B Virus (HBV) Genomes by an Endogenous Cytidine Deaminase inside HBV Cores Informs a Model of Reverse Transcription

Journal of Virology
Smita Nair, Adam Zlotnick

Abstract

Cytidine deaminases inhibit replication of a broad range of DNA viruses by deaminating cytidines on single-stranded DNA (ssDNA) to generate uracil. While several lines of evidence have revealed hepatitis B virus (HBV) genome editing by deamination, it is still unclear which nucleic acid intermediate of HBV is modified. Hepatitis B virus has a relaxed circular double-stranded DNA (rcDNA) genome that is reverse transcribed within virus cores from a RNA template. The HBV genome also persists as covalently closed circular DNA (cccDNA) in the nucleus of an infected cell. In the present study, we found that in HBV-producing HepAD38 and HepG2.2.15 cell lines, endogenous cytidine deaminases edited 10 to 25% of HBV rcDNA genomes, asymmetrically with almost all mutations on the 5' half of the minus strand. This region corresponds to the last half of the minus strand to be protected by plus-strand synthesis. Within this half of the genome, the number of mutations peaks in the middle. Overexpressed APOBEC3A and APOBEC3G could be packaged in HBV capsids but did not change the amount or distribution of mutations. We found no deamination on pregenomic RNA (pgRNA), indicating that an intact genome is encapsidated and deaminated during or after...Continue Reading

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Citations

Feb 26, 2019·Journal of Viral Hepatitis·Maria G MartinezFabien Zoulim
Sep 5, 2019·International Journal of Molecular Sciences·Nur K Mohd-IsmailYee-Joo Tan
May 30, 2020·Nature Reviews. Gastroenterology & Hepatology·Peter A RevillMargaret Littlejohn
Sep 24, 2020·International Journal of Molecular Sciences·Sergey BrezginVladimir Chulanov
Aug 17, 2020·PLoS Pathogens·Florian PoulainNicolas A Gillet
Dec 4, 2020·Microorganisms·Wendy Kaichun XuJaquelin P Dudley
May 30, 2021·Journal of Hepatology·Maria Guadalupe MartinezFabien Zoulim
Oct 31, 2018·Journal of the American Chemical Society·Smita NairAdam Zlotnick

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