Journal Article

APOBEC3 Proteins: From Antiviral Immunity to Oncogenic Drivers in HPV-Positive Cancers

Fortunato, Giulia Mariane, Biondo, Rosalba, Fenton, Timothy Robert, Trugilo, Kleber Paiva, Castilha, Eliza Pizarro, Oliveira, Karen Brajão de

2025

Overview

The human APOBEC superfamily consists of eleven cytidine deaminase enzymes. Among them, APOBEC3 enzymes play a dual role in antiviral immunity and cancer development. APOBEC3 enzymes, including APOBEC3A (A3A) and APOBEC3B (A3B), induce mutations in viral DNA, effectively inhibiting viral replication but also promoting somatic mutations in the host genome, contributing to cancer development. A3A and A3B are linked to mutational signatures in over 50% of human cancers, with A3A being a potent mutagen. A3B, one of the first APOBEC3 enzymes linked to carcinogenesis, plays a significant role in HPV-associated cancers by driving somatic mutagenesis and tumor progression. The A3A_B deletion polymorphism results in a hybrid A3A_B gene, leading to increased A3A expression and enhanced mutagenic potential. Such polymorphism has been linked to an elevated risk of certain cancers, particularly in populations where it is more prevalent. This review explores the molecular mechanisms of APOBEC3 proteins, highlighting their dual roles in antiviral defense and tumorigenesis. We also discuss the clinical implications of genetic variants, such as the A3A_B polymorphism, mainly in HPV infection and associated cancers, providing a comprehensive understanding of their contributions to both viral restriction and cancer development.

• Publisher: MDPI AG,MDPI
• Subject: Animals / APOBEC / APOBEC Deaminases - genetics / Apolipoproteins / Cancer / Carcinogenesis / Carcinogenesis - genetics / Chromosomes / Complications and side effects / Cytidine deaminase / Cytidine Deaminase - genetics / deamination / Development and progression / Diversification / DNA biosynthesis / DNA methylation / Editing / Enzymes / Epstein-Barr virus / Gene deletion / Gene expression / Genetic aspects / Genetic diversity / Genetic engineering / Genetic polymorphisms / Genomes / Health aspects / Hepatitis B / HIV / HPV / Human immunodeficiency virus / Human papillomavirus / Humans / Hydrolases / Immune system / Immunity / Immunity (Disease) / Infections / Interferon / Kaposis sarcoma / Liver cancer / Metabolism / Minor Histocompatibility Antigens - genetics / Molecular modelling / Mutagenesis / Mutation / Neoplasms - genetics / Neoplasms - immunology / Neoplasms - virology / Papillomaviridae - genetics / Papillomaviridae - immunology / Papillomavirus infections / Papillomavirus Infections - complications / Papillomavirus Infections - immunology / Papillomavirus Infections - virology / Physiological aspects / Polymorphism / Polymorphism, Genetic / Proteins / Review / Risk factors / Severe acute respiratory syndrome coronavirus 2 / Tumorigenesis / Viral infections