| Title | IFITM3 directly engages and shuttles incoming virus particles to lysosomes |
| Authors | Spence, Jennifer S. He, Ruina Hoffmann, Hans-Heinrich Das, Tandrila Thinon, Emmanuelle Rice, Charles M. Peng, Tao Chandran, Kartik Hang, Howard C. |
| Affiliation | Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA Rockefeller Univ, Lab Chem Biol & Microbial Pathogenesis, 1230 York Ave, New York, NY 10021 USA Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, 1230 York Ave, New York, NY 10021 USA Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen, Peoples R China |
| Issue Date | 2019 |
| Publisher | NATURE CHEMICAL BIOLOGY |
| Abstract | Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live-cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, IFITM2 and IFITM3 act cooperatively and function in a dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live-cell imaging studies, we show that IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live-cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation. |
| URI | http://hdl.handle.net/20.500.11897/550428 |
| ISSN | 1552-4450 |
| DOI | 10.1038/s41589-018-0213-2 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 深圳研究生院待认领 |
