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Journal of Virology, January 2005, p. 547-553, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.547-553.2005

Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway

Nancy J. Sullivan,1 Mary Peterson,1 Zhi-yong Yang,1 Wing-pui Kong,1 Heinricus Duckers,2,{dagger} Elizabeth Nabel,2 and Gary J. Nabel1*

Vaccine Research Center, National Institute for Allergy and Infectious Disease,1 National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland2

Received 26 April 2004/ Accepted 23 August 2004

Ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. Though GP, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie Ebola virus cytopathicity are poorly understood. Here, we define a cellular mechanism responsible for Ebola virus GP cytotoxicity. GP selectively decreased the expression of cell surface molecules that are essential for cell adhesion and immune function. GP dramatically reduced levels of {alpha}Vß3 without affecting the levels of {alpha}2ß1 or cadherin, leading to cell detachment and death. This effect was inhibited in vitro and in vivo by brefeldin A and was dependent on dynamin, the GTPase. GP also decreased cell surface expression of major histocompatibility complex class I molecules, which alters recognition by immune cells, and this effect was also dependent on the mucin domain previously implicated in GP cytotoxicity. By altering the trafficking of select cellular proteins, Ebola virus GP inflicts cell damage and may facilitate immune escape by the virus.

* Corresponding author: Mailing address: Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Dr., MSC-3005, Bethesda, MD 20814. Phone: (301) 496-1852. Fax: (301) 480-0274. E-mail: gnabel{at}nih.gov.

{dagger} Present address: Dept. of Cell Biology & Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands.

Journal of Virology, January 2005, p. 547-553, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.547-553.2005




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