RELEASE OF VIRAL GLYCOPROTEINS DURING EBOLA-VIRUS INFECTION

Maturation and release of the Ebola virus glycoprotein GP were studied in cells infected with either Ebola or recombinant vaccinia viruses. Significant amounts of GP were found in the culture medium in nonvirio n forms. The major form represented the large subunit GP(1) that was s hed after release of its disulfide linkage to the smaller transmembran e subunit GP(2). The minor form were intact GP(1,2) complexes incorpor ated into virosomes. Vector-expressed GP formed spikes morphologically indistinguishable from spikes on virus particles, indicating that spi ke assembly is independent of other viral proteins. Analysis of a trun cation mutant revealed an early and almost complete release of GP(1,2) molecules, showing that membrane anchoring is mediated by the carboxy -terminal hydrophobic domain of GP(2). We have also compared wild-type virus which requires transcriptional editing for synthesis of full-le ngth GP with a variant that does not depend on editing. Both viruses r eleased comparable amounts of GP(1), but the variant expressed only mi nute amounts of the small, soluble GP which is the expression product of nonedited mRNA species of the GP gene. The abundant shedding of sol uble GP(1) may play an important role in the immunopathology of Ebola hemorrhagic fever in experimentally and naturally infected hosts, (C) 1998 Academic Press.