Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses.
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.
Garbutt
Michael
M
Special Pathogens Program, National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba, Canada R3E 3R2.
Liebscher
Ryan
R
Wahl-Jensen
Victoria
V
Jones
Steven
S
Möller
Peggy
P
Wagner
Ralf
R
Volchkov
Viktor
V
Klenk
Hans-Dieter
HD
Feldmann
Heinz
H
Ströher
Ute
U
D000818:Animals; D018050:Arenavirus / Q000737:chemistry*; D005260:Female; D016563:Filoviridae / Q000737:chemistry*; D005822:Genetic Vectors / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000096:biosynthesis*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication
D006023:Glycoproteins; D011994:Recombinant Proteins; D014764:Viral Proteins