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, w e have established a system that allows the recovery of infectious virus fr om cloned cDNA and thus permits genetic manipulation. We created a mutant i n which the editing site of the gene encoding envelope glycoprotein (CP) wa s eliminated. This mutant no longer expressed the nonstructural glycoprotei n sGP, Synthesis of CP increased, but most of it accumulated in the endopla smic reticulum as immature precursor. The mutant was significantly more cyt otoxic than wild-type virus, indicating that cytotoxicity caused by CP is d own-regulated by the virus through transcriptional RNA editing and expressi on of sGP.