APOBEC3F restricts PRRSV replication through its CD2 domain and interaction with host antiviral proteins.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen that causes substantial economic losses to the global swine industry. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 F (APOBEC3F), a key constituent of cytoplasmic processing bodies (P-bodies) and a member of the deaminase protein family, possesses intrinsic antiviral activity. This study systematically investigates the effects of APOBEC3F and its functional domains on PRRSV replication. This study systematically investigated the effects of APOBEC3F and its functional domains on PRRSV replication. We found that overexpression of APOBEC3F and its C-terminal deaminase domain (CD2) markedly suppressed PRRSV replication (including transcription, protein expression, and viral titers) in susceptible porcine cells. Conversely, APOBEC3F knockdown enhanced viral replication. Notably, several PRRSV proteins-NSP1α, NSP1β, NSP5, NSP7, GP4, GP5, and N-were found to downregulate endogenous APOBEC3F mRNA expression in host cells. Moreover, IP-MS analysis identified several potential candidate interactors, including DEAD-box helicases (such as DDX6 and MOV10) and other host factors, suggesting that APOBEC3F may associate with P-body components to exert its antiviral function. These results offer new insights into the molecular mechanisms of APOBEC3F-mediated antiviral defense against PRRSV and underscore its potential as a therapeutic target.