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

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• The APOBEC superfamily comprises eleven cytidine deaminases.
• APOBEC3 (A3) enzymes are crucial in antiviral immunity and cancer development.
• A3A and A3B enzymes induce mutations in viral DNA, inhibiting replication but also causing somatic mutations in the host genome.

Purpose of the Study:

• To explore the molecular mechanisms of APOBEC3 proteins.
• To highlight the dual roles of A3 enzymes in antiviral defense and tumorigenesis.
• To discuss clinical implications of genetic variants, especially the A3A_B polymorphism, in HPV infection and associated cancers.

Main Methods:

• Literature review of APOBEC3 enzyme functions.
• Analysis of molecular mechanisms of mutagenesis.
• Examination of genetic variants and their association with cancer risk.
• Focus on Human Papillomavirus (HPV) infection and related cancers.

Main Results:

• A3A and A3B are linked to mutational signatures in over 50% of human cancers.
• A3A is a potent mutagen, and A3B drives mutagenesis in HPV-associated cancers.
• The A3A_B deletion polymorphism leads to increased A3A expression and mutagenic potential, elevating cancer risk.

Conclusions:

• APOBEC3 enzymes exhibit a dual role in viral restriction and cancer development.
• Genetic variants, such as the A3A_B polymorphism, significantly impact cancer risk, particularly in HPV-associated malignancies.
• Understanding these mechanisms is vital for comprehending viral pathogenesis and cancer progression.