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 nonvirion forms. The major form represented the large subunit GP1 that was shed after release of its disulfide linkage to the smaller transmembrane subunit GP2. The minor form were intact GP1,2 complexes incorporated into virosomes. Vector-expressed GP formed spikes morphologically indistinguishable from spikes on virus particles, indicating that spike assembly is independent of other viral proteins. Analysis of a truncation mutant revealed an early and almost complete release of GP1,2 molecules, showing that membrane anchoring is mediated by the carboxy-terminal hydrophobic domain of GP2. We have also compared wild-type virus which requires transcriptional editing for synthesis of full-length GP with a variant that does not depend on editing. Both viruses released comparable amounts of GP1, but the variant expressed only minute amounts of the small, soluble GP which is the expression product of nonedited mRNA species of the GP gene. The abundant shedding of soluble GP1 may play an important role in the immunopathology of Ebola hemorrhagic fever in experimentally and naturally infected hosts.
The oligosaccharide side chains of the glycoprotein of Marburg virus (MW 170,000) have been analyzed by determining their sensitivity to enzymatic degradation and their reactivity with lectins. It was found that they consist of N- and O-glycans. Studies employing chemical cross-linking showed that the glycoprotein is present as a homotrimer in the viral envelope.
The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.
Forty years ago, in early August 1967, the first filovirus ever detected, Marburg virus, made its appearance in Europe, causing severe and often fatal hemorrhagic fever in laboratory workers in Marburg and Frankfurt and, about 4 weeks later, in Belgrade. The etiological agent was isolated and identified by the combined efforts of virologists in Marburg and Hamburg within the very short time of 3 months. Marburg was not the only town where the virus was isolated and identified for the first time, but most cases of infection occurred in Marburg.
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