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Journal of Virology, May 2004, p. 5458-5465, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5458-5465.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses

Michael Garbutt,1,{dagger} Ryan Liebscher,1,{dagger} Victoria Wahl-Jensen,1,2 Steven Jones,1,3 Peggy Möller,1,4 Ralf Wagner,4 Viktor Volchkov,4,5 Hans-Dieter Klenk,4 Heinz Feldmann,1,2* and Ute Ströher1,2*

Special Pathogens Program, National Microbiology Laboratory, Health Canada,1 Department of Medical Microbiology and Infectious Diseases,2 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada,3 Institute of Virology, Philipps University, Marburg, Germany,4 Filovirus Laboratory, INSERM U412, University Claude Bernard Lyon-1, Lyon, France5

Received 12 November 2003/ Accepted 14 January 2004

Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (Marburg virus, Ebola virus, and Lassa virus) were generated and characterized. All recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. Unlike the rVSVs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the foreign transmembrane glycoproteins in replacement of the VSV glycoprotein were slightly attenuated in growth. Biosynthesis and processing of the foreign glycoproteins were authentic, and the cell tropism was defined by the transmembrane glycoprotein. None of the rVSVs displayed pathogenic potential in animals. The rVSV expressing the Zaire Ebola virus transmembrane glycoprotein mediated protection in mice against a lethal Zaire Ebola virus challenge. Our data suggest that the recombinant VSV can be used to study the role of the viral glycoproteins in virus replication, immune response, and pathogenesis.

* Corresponding author. Mailing address: Special Pathogens Program, National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba, Canada R3E 3R2. Phone for Ute Ströher: (204) 789-5070. Fax: (204) 789-2140. E-mail: Ute_Stroeher{at}hc-sc.gc.ca. Phone for Heinz Feldmann: (204) 789-6019. Fax: (204) 789-2140. E-mail: Heinz_Feldmann{at}hc-sc.gc.ca.

{dagger} M.G. and R.L. contributed equally to this work.

Journal of Virology, May 2004, p. 5458-5465, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5458-5465.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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