PT - JOURNAL ARTICLE AU - Wing-Yiu Jason Lee AU - Chen Liang AU - Richard D Sloan TI - IFITM proteins inhibit HIV-1 protein synthesis AID - 10.1101/201525 DP - 2018 Jan 01 TA - bioRxiv PG - 201525 4099 - http://biorxiv.org/content/early/2018/04/11/201525.short 4100 - http://biorxiv.org/content/early/2018/04/11/201525.full AB - 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.