Mpox Evolution: Has the Current Outbreak Revealed a Pox on "U"?

The recent mpox (monkeypox) outbreak has prompted genomic studies to track global spread of the disease. These studies have also revealed unexpected patterns of mutations that implicate the action of the immune defense APOBEC3 family of enzymes, which catalyze conversion of cytosine (C) to uracil (U) in DNA, in viral evolution. As poxviruses have conventionally been regarded as slow-evolving viruses, the rapid emergence of APOBEC3 mutational signatures begs a series of important and open questions regarding how host-pathogen interactions may have changed and whether these mutations are bystanders or have roles in pathogenesis.