NPF motifs in the vaccinia virus protein A36 recruit intersectin-1 to promote Cdc42:N-WASP-mediated viral release from infected cells
| Autor: | Xenia Snetkov, Ina Weisswange, Michael Way, Julia Pfanzelter, Ashley C. Humphries |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Viral protein viruses Immunology Endocytic cycle Amino Acid Motifs Vaccinia virus macromolecular substances medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Clathrin Virus 03 medical and health sciences chemistry.chemical_compound Genetics medicine Humans cdc42 GTP-Binding Protein Virus Release Adaptor Proteins Signal Transducing Viral Structural Proteins biology Signal transducing adaptor protein Cell Biology Intersectin-1 Virology Actins Adaptor Proteins Vesicular Transport 030104 developmental biology chemistry Host-Pathogen Interactions biology.protein Vaccinia Wiskott-Aldrich Syndrome Protein HeLa Cells Protein Binding |
| Zdroj: | Nature microbiology. 1(10) |
| ISSN: | 2058-5276 |
| Popis: | During its egress, vaccinia virus transiently recruits AP-2 and clathrin after fusion with the plasma membrane. This recruitment polarizes the viral protein A36 beneath the virus, enhancing actin polymerization and the spread of infection. We now demonstrate that three NPF motifs in the C-terminus of A36 recruit AP-2 and clathrin by interacting directly with the Epsin15 homology domains of Eps15 and intersectin-1. A36 is the first identified viral NPF motif containing protein shown to interact with endocytic machinery. Vaccinia still induces actin tails in the absence of the A36 NPF motifs. Their loss, however, reduces the cell-to-cell spread of vaccinia. This is due to a significant reduction in virus release from infected cells, as the lack of intersectin-1 recruitment leads to a loss of Cdc42 activation, impairing N-WASP-driven Arp2/3-mediated actin polymerization. Our results suggest that initial A36-mediated virus release plays a more important role than A36-driven super-repulsion in promoting the cell-to-cell spread of vaccinia. |
| Databáze: | OpenAIRE |
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