Influenza virus enters cells by endocytosis, and requires the low pH of the late endosome for successful infection. Here, we investigated the requirements for sorting into the multivesicular body pathway of endocytosis. We show that treatment of host cells with the proteasome inhibitors MG132 and lactacystin directly affects the early stages of virus replication. Unlike other viruses, such as retroviruses, influenza virus budding was not affected. The requirement for proteasome function was not shared by two other pH-dependent viruses: Semliki Forest virus and vesicular stomatitis virus. With MG132 treatment, incoming influenza viruses were retained in endosomes that partially colocalized with mannose 6-phosphate receptor, but not with classical markers of early or late endosomes. Colocalization was also observed with Rme-1, which is part of the recycling pathway of endocytosis. In addition, influenza virus entry was dependent on the vacuolar protein sorting pathway, as over-expression of dominant-negative hVPS4 caused arrest of viruses in endosome-like populations that partially colocalized with the hVPS4 protein. Overall, we conclude that influenza virus selectively requires the ubiquitin/vacuolar protein sorting pathway for entry into host cells, and that it must communicate with a specific cellular machinery for intracellular sorting during the initial phase of virus infection.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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