APOBEC3 Proteins Inhibit LINE‐1 Retrotransposition in the Absence of ORF1p Binding

Members of the apolipoprotein B mRNA editing complex polypeptide 1‐like (APOBEC) family of enzymes exhibit inhibitory activity against a variety of exogenous and endogenous retroviruses including retrotransposons, such as long interspersed element 1 (LINE‐1). Indeed, human APOBEC3A, APOBEC3B, and APOBEC3F inhibit retrotransposition of human LINE‐1, mouse IAP and MusD retrotransposons. In our study, we examined whether the inhibitory effect of APOBEC3 proteins correlates with APOBEC3 ability to bind the LINE‐1 ORF1 protein. We examined the interactions between the LINE‐1 ORF1 protein and the most potent LINE‐1 retrotransposon inhibitors, human APOBEC3A and APOBEC3B, by immunofluorescence and immunoprecipitation. Although human APOBEC3A shows the highest inhibitory potency against LINE‐1 retrotransposon, no direct interactions were identified either by immunofluorescence or by co‐immunoprecipitation. APOBEC3B binds to LINE‐1 ORF1 protein, yet no co‐localization was detected. We concluded that APOBEC3 proteins interfere indirectly with the LINE‐1 retrotransposition pathway, probably through interference with RNA targeting.