IFITM3 Restricts Human Metapneumovirus Infection
| Autor: | Ashley Zani, Adam D. Kenney, Lizhi Zhang, Temet M. McMichael, Jacob S. Yount, Mijia Lu, Jianrong Li, Mahesh Chemudupati, Yu Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Endosome viruses Endocytosis Endosome membrane Virus Major Articles and Brief Reports 03 medical and health sciences Human metapneumovirus Chlorocebus aethiops Animals Humans Immunology and Allergy Vero Cells Paramyxoviridae Infections biology Chemistry Membrane Proteins RNA-Binding Proteins virus diseases Lipid bilayer fusion Virus Internalization biology.organism_classification Virology Transmembrane protein respiratory tract diseases Endosome localization HEK293 Cells 030104 developmental biology Infectious Diseases Toll-Like Receptor 7 A549 Cells Host-Pathogen Interactions Metapneumovirus |
| Zdroj: | The Journal of Infectious Diseases. |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiy361 |
| Popis: | Human metapneumovirus (hMPV) utilizes a bifurcated cellular entry strategy, fusing either with the plasma membrane or, after endocytosis, with the endosome membrane. Whether cellular factors restrict or enhance either entry pathway is largely unknown. We found that the interferon-induced transmembrane protein 3 (IFITM3) inhibits hMPV infection to an extent similar to endocytosis-inhibiting drugs, and an IFITM3 variant that accumulates at the plasma membrane in addition to its endosome localization provided increased virus restriction. Mechanistically, IFITM3 blocks hMPV F protein-mediated membrane fusion, and inhibition of infection was reversed by the membrane destabilizing drug amphotericin B. Conversely, we found that infection by some hMPV strains is enhanced by the endosomal protein toll-like receptor 7 (TLR7), and that IFITM3 retains the ability to restrict hMPV infection even in cells expressing TLR7. Overall, our results identify IFITM3 as an endosomal restriction factor that limits hMPV infection of cells. |
| Databáze: | OpenAIRE |
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