Human Schlafen 11 exploits codon preference discrimination to attenuate viral protein synthesis of prototype foamy virus (PFV)

Highlights: • Human SLFN11 inhibits PFV replication via a codon-usage-related translational mechanism. • SLFN11 from cattle and African green monkey also suppresses PFV replication. • The ATPase activity and helicase activity of SLFN11 are involved in its anti-PFV activity. • Dephosphorylation of SLFN11 is essential for its anti-PFV activity. Recently, the Schlafen (SLFN) proteins have been identified as a novel interferon-stimulated family with antiviral properties. In this study, we reported that SLFN11 inhibited prototype foamy virus (PFV) replication. Over-expression of human SLFN11 reduced viral production, while knockdown of SLFN11 enhanced viral infectivity. In addition, SLFN11 from cattle and African green monkey also suppressed PFV production. Both the ATPase activity and helicase activity of SLFN11 were required for its inhibitory function. Dephosphorylation activated the antiviral activity of SLFN11. More importantly, SLFN11 inhibited the expression of viral protein, which was rescued by viral gene codon optimization. Together, our results demonstrated that SLFN11 impaired PFV viral protein synthesis by exploiting the distinct codon usage between the virus and the host. These findings further broaden our understanding of the antiviral properties of the SLFN family and the molecular mechanism of PFV latent infection.