TY - JOUR T1 - IFITM proteins inhibit HIV-1 protein synthesis JF - bioRxiv DO - 10.1101/201525 SP - 201525 AU - Wing-Yiu Jason Lee AU - Chen Liang AU - Richard D Sloan Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/04/11/201525.abstract N2 - Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef. ER -