Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence.
The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than Zaire GP. Sequential removal of regions of potential O-linked glycosylation at the C terminus of GP1 led to a step-wise reduction in cell detachment without obviously affecting GP function, suggesting that such modifications are involved in inducing the detachment phenotype. While causing cell rounding and detachment in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed, following transient expression of GP, cells were able to readhere and continue to divide. Also, the rounding effect was not limited to 293T cells. Replication-deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell adhesion in a range of cell lines and primary cell types, including those with proposed relevance to Ebola virus infection in vivo, such as endothelial cells and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a reduction in cell surface expression of adhesion molecules such as integrin beta1 concurrent with the loss of cell adhesion was observed. A number of other cell surface molecules, however, including major histocompatibility complex class I and the epidermal growth factor receptor, were also down-modulated, suggesting a global mechanism for surface molecule down-regulation.
Simmons
Graham
G
Department of Microbiology, School of Medicine, University of Pennsylvania, 303A Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Wool-Lewis
Rouven J
RJ
Baribaud
Frédéric
F
Netter
Robert C
RC
Bates
Paul
P
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D006224:Cricetinae; D015536:Down-Regulation; D029043:Ebolavirus / Q000378:metabolism / Q000472:pathogenicity*; D004727:Endothelium / Q000166:cytology; D019142:Hemorrhagic Fever, Ebola / Q000821:virology; D006801:Humans; D008264:Macrophages; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus