DHX15 inhibits mouse APOBEC3 deamination activity

APOBEC3 family proteins are critical host proteins that counteract and prevent the replication
of retroviruses and other viruses through cytidine deamination. Human APOBEC3G inactivates
HIV-1 through the introduction of lethal mutations to viral genomes. In contrast, mouse
APOBEC3 does not induce DNA hypermutation of murine retroviruses, although it retains
functional cytidine deaminase activity. Why mouse APOBEC3 does not effectively deaminate
MLV is still unknown. In this study, we found that the dead box helicase DHX15 interacts with
mouse APOBEC3 and inhibits its deamination activity. DHX15 was packaged into virions
independent of its binding with APOBEC3. Moreover, DHX15 knockdown inhibited MLV
replication and resulted in more G-to-A mutations in proviral DNA. Finally, DHX15 knockdown
induced DNA damage in murine cells, suggesting that it plays a role in preserving genome
integrity in cells expressing mouse APOBEC3 protein.