Overlapping functions of APOBEC enzymes in antiviral immunity and cancer

Abstract

APOBEC enzymes are a family of innate antiviral enzymes that form an important barrier against DNA-based pathogens. Encoding and expressing these DNA mutating enzymes, however, is an inherently risky endeavor for the stability of the host genome if not regulated appropriately. These risks have been demonstrated in numerous cancers where APOBEC3B is overexpressed and the APOBEC-associated mutation signature is enriched. Emphasizing the importance of this observation, elevated expression of APOBEC3B and presence of APOBEC-associated mutations has now been consistently linked to aggressive phenotypes and worse outcome in cancer patients. Here I present data demonstrating overlapping functions of APOBEC3 enzymes in antiviral immunity and cancer. In both of these models, APOBEC3 enzymes contribute potentially deleterious and beneficial mutations potentially impacting the survival of tumors and viruses. Additionally, the functions of these enzymes can be modulated by heritable germline mutations in the APOBEC3 locus and viral infections. DNA viruses can also act as valuable molecular probes into the regulation of APOBEC3 enzymes in tumors leading to the development of better therapies.