mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3
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
DOI:
10.1073/pnas.1811892115
Publication Date:
2018-10-09T15:50:07Z
AUTHORS (4)
ABSTRACT
SignificanceGene delivery by virus-like particles holds enormous therapeutic potential to correct inherited genetic disorders and to prevent infectious disease. However, cells express antiviral factors that prevent virus infection and, consequently, limit the success of gene therapy. Here, we reveal the mechanism by which the drug rapamycin improves lentivirus-mediated gene delivery. Rapamycin treatment led to degradation of IFITM3, a broad and potent antiviral protein which inhibits virus entry into cells. IFITM3 is selectively cleared from endosomes, the sites where viral and cellular membranes fuse, and is sorted for disposal in lysosomes. While revealing an immunosuppressive function with clinical benefits, we caution that rapamycin use in humans may facilitate infection by pathogenic viruses like Influenza A virus.
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