mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3

• DOI: 10.1073/pnas.1811892115
• Publication Date: 2018-10-09T15:50:07Z
• Authors: Guoli Shi; Stosh Ozog; Bruce E. Torbett; Alex A. Compton
• Keywords: Sirolimus; 0301 basic medicine; 0303 health sciences; Multidisciplinary; TOR Serine-Threonine Kinases; Membrane Proteins; RNA-Binding Proteins; Endosomes; Virus Internalization; Antiviral Agents; 7. Clean energy; Cell Line; 3. Good health; Protein Transport; 03 medical and health sciences; HEK293 Cells; PNAS Plus; Virus Diseases; Cell Line, Tumor; Host-Pathogen Interactions; Humans; HeLa Cells

Significance Gene delivery by virus-like particles holds enormous therapeutic potential to correct inherited genetic disorders and prevent infectious disease. However, cells express antiviral factors that virus infection and, consequently, limit the success of gene therapy. Here, we reveal mechanism which drug rapamycin improves lentivirus-mediated delivery. Rapamycin treatment led degradation IFITM3, a broad potent protein inhibits entry into cells. IFITM3 is selectively cleared from endosomes, sites where viral cellular membranes fuse, sorted for disposal in lysosomes. While revealing an immunosuppressive function with clinical benefits, caution use humans may facilitate pathogenic viruses like Influenza A virus.