Differential induction of cellular detachment by envelope glycoproteins of Marburg and Ebola (Zaire) viruses.
Human infection by Marburg (MBG) or Ebola (EBO) virus is associated with fatal haemorrhagic fevers. While these filoviruses may both incite disease as a result of explosive virus replication, we hypothesized that expression of individual viral gene products, such as the envelope glycoprotein (GP), may directly alter target cells and contribute to pathogenesis. We found that expression of EBO GP in 293T cells caused significant levels of cellular detachment in the absence of cell death or virus replication. This detachment was induced most potently by membrane-bound EBO GP, rather than the shed glycoprotein products (sGP or GP1), and was largely attributable to a domain within the extracellular region of GP2. Furthermore, detachment was blocked by the Ser/Thr kinase inhibitor 2-aminopurine, suggesting the importance of a phosphorylation-dependent signalling cascade in inducing detachment. Since MBG GP did not induce similar cellular detachment, MBG and EBO GP interact with target cells by distinct processes to elicit cellular dysregulation.
Chan
Stephen Y
SY
Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, CA 94141-9100, USA2.|Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, CA 94141-9100, USA1.
Ma
Melissa C
MC
Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, CA 94141-9100, USA1.
Goldsmith
Mark A
MA
Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, CA 94141-9100, USA2.|Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, CA 94141-9100, USA1.
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000472:pathogenicity*; D004591:Electrophoresis, Polyacrylamide Gel; D015686:Gene Products, env / Q000235:genetics / Q000502:physiology; D006041:Goats; D006168:Guinea Pigs; D029024:Marburgvirus / Q000472:pathogenicity*; D015398:Signal Transduction; D014709:Vero Cells
D015686:Gene Products, env