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Release of Immunomodulatory Ebola Virus Glycoprotein-Containing Microvesicles Is Suppressed by Tetherin in a Species-Specific Manner
The Ebola virus glycoprotein (EBOV-GP) forms GP-containing microvesicles, so-called virosomes, which are secreted from GP-expressing cells. However, determinants of GP-virosome release and their functionality are poorly understood. We characterized GP-mediated virosome formation and delineated the r...
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Published in: | Cell reports (Cambridge) 2019-02, Vol.26 (7), p.1841-1853.e6 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | The Ebola virus glycoprotein (EBOV-GP) forms GP-containing microvesicles, so-called virosomes, which are secreted from GP-expressing cells. However, determinants of GP-virosome release and their functionality are poorly understood. We characterized GP-mediated virosome formation and delineated the role of the antiviral factor tetherin (BST2, CD317) in this process. Residues in the EBOV-GP receptor-binding domain (RBD) promote GP-virosome secretion, while tetherin suppresses GP-virosomes by interactions involving the GP-transmembrane domain. Tetherin from multiple species interfered with GP-virosome release, and tetherin from the natural fruit bat reservoir showed the highest inhibitory activity. Moreover, analyses of GP from various ebolavirus strains, including the EBOV responsible for the West African epidemic, revealed the most efficient GP-virosome formation by highly pathogenic ebolaviruses. Finally, EBOV-GP-virosomes were immunomodulatory and acted as decoys for EBOV-neutralizing antibodies. Our results indicate that GP-virosome formation might be a determinant of EBOV immune evasion and pathogenicity, which is suppressed by tetherin.
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•The Ebola virus glycoprotein (GP) drives the release of GP-containing virosomes•Tetherin restricts GP-virosome release through transmembrane domain interactions•GP-virosome release is most efficient for GPs of highly pathogenic Ebola viruses•Immunomodulatory GP-virosomes serve as decoys for EBOV-neutralizing antibodies
Nehls et al. demonstrate that the glycoprotein of the highly pathogenic Ebola virus is incorporated into secretory vesicles, called GP-virosomes, to dampen the immune response and capture neutralizing antibodies. The lack of replication competence and the incorporation of antigenically intact GP might qualify GP-virosomes as safe vaccine candidates. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2019.01.065 |