A polymorphism within the internal fusion loop of the Ebola virus glycoprotein modulates host cell entry.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two non-human primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency. We found that EBOV2014-GP-driven entry into diverse NHP-derived cell lines as well as human monocyte-derived macrophages and dendritic cells was reduced as compared to EBOV1976-GP, although entry into most human- and all bat-derived cell lines tested was comparable. Moreover, EBOV2014 replication in NHP but not human cells was diminished relative to EBOV1976, suggesting that reduced cell entry translated into reduced viral spread. Mutagenic analysis of EBOV2014-GP and EBOV1976-GP revealed that an amino acid polymorphism in the receptor-binding domain, A82V, modulated entry efficiency in a cell line-independent manner and did not account for the reduced EBOV2014-GP-driven entry into NHP cells. In contrast, polymorphism T544I, located in the internal fusion loop in the GP2 subunit, was found to be responsible for the entry phenotype. These results suggest that position 544 is an important determinant of EBOV infectivity for NHP- and certain human target cells.IMPORTANCE The Ebola virus disease outbreak in West Africa in 2013 entailed more than 10,000 deaths. The scale of the outbreak and its dramatic impact on human health raised the question whether the responsible virus was particularly adept at infecting human cells. Our study shows that an amino acid exchange, A82V, that the virus acquired during the epidemic and that was not observed in previously circulating viruses, increases viral entry into diverse target cells. In contrast, the epidemic virus showed a reduced ability to enter cells of non-human primates as compared to the virus circulating in 1976 and a single amino acid exchange in the internal fusion loop of the viral glycoprotein was found to account for this phenotype.
CitationA polymorphism within the internal fusion loop of the Ebola virus glycoprotein modulates host cell entry. 2017 J. Virol.
AffiliationTwincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
JournalJournal of virology
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Spontaneous Mutation at Amino Acid 544 of the Ebola Virus Glycoprotein Potentiates Virus Entry and Selection in Tissue Culture.
- Authors: Ruedas JB, Ladner JT, Ettinger CR, Gummuluru S, Palacios G, Connor JH
- Issue date: 2017 Aug 1
- Functional Characterization of Adaptive Mutations during the West African Ebola Virus Outbreak.
- Authors: Dietzel E, Schudt G, Krähling V, Matrosovich M, Becker S
- Issue date: 2017 Jan 15
- Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.
- Authors: Diehl WE, Lin AE, Grubaugh ND, Carvalho LM, Kim K, Kyawe PP, McCauley SM, Donnard E, Kucukural A, McDonel P, Schaffner SF, Garber M, Rambaut A, Andersen KG, Sabeti PC, Luban J
- Issue date: 2016 Nov 3
- Shedding of Ebola Virus Surface Glycoprotein Is a Mechanism of Self-regulation of Cellular Cytotoxicity and Has a Direct Effect on Virus Infectivity.
- Authors: Dolnik O, Volchkova VA, Escudero-Perez B, Lawrence P, Klenk HD, Volchkov VE
- Issue date: 2015 Oct 1
- Growth-Adaptive Mutations in the Ebola Virus Makona Glycoprotein Alter Different Steps in the Virus Entry Pathway.
- Authors: Ruedas JB, Arnold CE, Palacios G, Connor JH
- Issue date: 2018 Oct 1