Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity.
To study the mechanisms underlying the high pathogenicity of Ebola virus, we have established a system that allows the recovery of infectious virus from cloned cDNA and thus permits genetic manipulation. We created a mutant in which the editing site of the gene encoding envelope glycoprotein (GP) was eliminated. This mutant no longer expressed the nonstructural glycoprotein sGP. Synthesis of GP increased, but most of it accumulated in the endoplasmic reticulum as immature precursor. The mutant was significantly more cytotoxic than wild-type virus, indicating that cytotoxicity caused by GP is down-regulated by the virus through transcriptional RNA editing and expression of sGP.
Volchkov
V E
VE
Institut für Virologie, Philipps-Universität, Robert-Koch-Strasse 17, 35037 Marburg, Germany. viktor.volchkov@ens-lyon.fr
Volchkova
V A
VA
Muhlberger
E
E
Kolesnikova
L V
LV
Weik
M
M
Dolnik
O
O
Klenk
H D
HD
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003588:Cytopathogenic Effect, Viral; D018076:DNA, Complementary; D029043:Ebolavirus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D017393:RNA Editing; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins; D014774:Virulence; D014779:Virus Replication
D018076:DNA, Complementary; D006023:Glycoproteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C113189:envelope glycoprotein, Ebola virus; C110613:secreted glycoprotein, Ebola virus