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Journal of Virology, March 2001, p. 2324-2330, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2324-2330.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Infectivity-Enhancing Antibodies to Ebola Virus Glycoprotein

Ayato Takada,1,2,dagger Shinji Watanabe,2 Katsunori Okazaki,1 Hiroshi Kida,1 and Yoshihiro Kawaoka2,3,*

Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818,1 and Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639,3 Japan, and Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin---Madison, Madison, Wisconsin 537062

Received 27 June 2000/Accepted 2 November 2000

Ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. Here we show that antisera produced by DNA immunization with a plasmid encoding the surface glycoprotein (GP) of the Zaire strain of Ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with the GP. Substantially weaker enhancement was observed with antiserum to the GP of the Reston strain, which is much less pathogenic in humans than the Ebola Zaire and Sudan viruses. The enhancing activity was abolished by heat but was increased in the presence of complement system inhibitors, suggesting that heat-labile factors other than the complement system are required for this effect. We also generated an anti-Zaire GP monoclonal antibody that enhanced viral infectivity and another that neutralized it, indicating the presence of distinct epitopes for these properties. Our findings suggest that antibody-dependent enhancement of infectivity may account for the extreme virulence of the virus. They also raise issues about the development of Ebola virus vaccines and the use of passive prophylaxis or therapy with Ebola virus GP antibodies.

* Corresponding author. Mailing address: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin---Madison, 2015 Linden Dr. West, Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. Email: kawaokay{at}svm.vetmed.wisc.edu.

dagger Present address: Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Journal of Virology, March 2001, p. 2324-2330, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2324-2330.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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