Ebola Virus Glycoprotein Promotes Enhanced Viral Egress by Preventing Ebola VP40 From Associating With the Host Restriction Factor BST2/Tetherin
| Autor: | Jean K. Gustin, Janet L. Douglas, Ashlee V. Moses, Ying Bai |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
viruses
Down-Regulation Receptors Cell Surface Biology medicine.disease_cause GPI-Linked Proteins Cell Line Viral Matrix Proteins Viral Proteins Immune system VP40 Viral envelope Antigens CD medicine Immunology and Allergy Humans Ebola and Marburg Viruses-Research Outbreak Management Epidemiology and Ecology Receptor Virus Release Glycoproteins chemistry.chemical_classification Innate immune system Ebola virus Mucins virus diseases Ebolavirus Virology Infectious Diseases HEK293 Cells chemistry Mutation Tetherin Glycoprotein |
| Zdroj: | The Journal of infectious diseases. 212 |
| ISSN: | 1537-6613 |
| Popis: | Background BST2/tetherin is an innate immune molecule with the unique ability to restrict the egress of human immunodeficiency virus (HIV) and other enveloped viruses, including Ebola virus (EBOV). Coincident with this discovery was the finding that the HIV Vpu protein down-regulates BST2 from the cell surface, thereby promoting viral release. Evidence suggests that the EBOV envelope glycoprotein (GP) also counteracts BST2, although the mechanism is unclear. Results We find that total levels of BST2 remain unchanged in the presence of GP, whereas surface BST2 is significantly reduced. GP is known to sterically mask surface receptors via its mucin domain. Our evaluation of mutant GP molecules indicate that masking of BST2 by GP is probably responsible for the apparent surface BST2 down-regulation; however, this masking does not explain the observed virus-like particle egress enhancement. We discovered that VP40 coimmunoprecipitates and colocalizes with BST2 in the absence but not in the presence of GP. Conclusions These results suggest that GP may overcome the BST2 restriction by blocking an interaction between VP40 and BST2. Furthermore, we have observed that GP may enhance BST2 incorporation into virus-like particles. Understanding this novel EBOV immune evasion strategy will provide valuable insights into the pathogenicity of this deadly pathogen. |
| Databáze: | OpenAIRE |
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