Antiviral and Mutagenic Effects of APOBEC Deaminases A3C, A3D, and A3H in a Hepatitis B Virus Model

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Ivan V. Karandashov^1,2,a*#, Sergey A. Brezgin^1,2#, Natalia I. Ponomareva^3#, Andrey S. Tikhonov^3,4, Vladimir P. Chulanov^2,3,5, Dmitry S. Kostyushev^1,2,6, and Anastasiya P. Kostyusheva¹

¹Laboratory of Genetic Technologies in Drug Development, E. I. Martsinovsky Institute of Medical Parasitology, Tropical and Transmissible Diseases, Sechenov University, 119435 Moscow, Russia

²Center for Precision Genome Editing, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

³Laboratory of Experimental Therapy of Infectious Diseases, E. I. Martsinovsky Institute of Medical Parasitology, Tropical and Transmissible Diseases, Sechenov University, 119435 Moscow, Russia

⁴Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia

⁵Department of Infectious Diseases, Sechenov University, 119435 Moscow, Russia

⁶Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119192 Moscow, Russia

^* To whom correspondence should be addressed.

^# These authors contributed equally to the work.

Received: October 10, 2025; Revised: November 30, 2025; Accepted: December 1, 2025

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Hepatitis B virus (HBV) infects human hepatocytes, causing acute or chronic liver infection. Chronic HBV infection leads to progressive liver damage, potentially resulting in cirrhosis or hepatocellular carcinoma. One promising antiviral strategy involves activating cytidine deaminases of the APOBEC/AID family, which could induce mutational degradation of HBV. Using a CRISPRa-based transcriptional activation system with modified sgRNAs, we investigated antiviral and oncogenic effects of the activating genes encoding APOBEC3C, APOBEC3D, and APOBEC3H.

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KEY WORDS: hepatitis B virus, HBV cccDNA, CRISPR activation, APOBEC3C, APOBEC3D, APOBEC3H

DOI: 10.1134/S0006297925603326

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