Putting Ebola Virus to Good Use--
Retroviruses, through the process of pseudotyping, can acquire the glycoproteins of certain other enveloped viruses and can utilize them for entry into cells. We have demonstrated, for example, that the Ebola virus glycoprotein can be incorporated into replication-defective retroviruses and that it can mediate viral entry into cells. Our experiments allow us to study the entry of viruses such as the Ebola and Marburg viruses in a fashion that is independent of the other steps in the viral life cycle and to do so in a safe and quantitative manner. Our pseudotyped viruses may also have applications in gene-transfer and gene-therapy experiments.
Using the system that we have developed, we have found, for example, that the biochemistry of Ebola virus entry resembles that of bird retroviruses. Our research supports the hypothesis that these viruses shared a common ancestor. This indicates that it is likely that the Ebola virus either currently has a bird as its natural host or that it has evolved from a bird virus. The idea that the natural reservoir for Ebola virus is a migratory African bird is consistent with the epidemiology of Ebola virus outbreaks. Biodefense Ebola virus Bioterrorism
Our studies have also allowed us to determine the disulfide-bond map of the Ebola glycoprotein and to propose that reduction of the disulfide bond between the two subunits of the Ebola glycoprotein complex, GP1 and GP2, is a critical step in the entry of Ebola virus into cells. Furthermore, we have shown that removal of a region of O-glycosylation of the protein enhances processing and its incorporation into recombinant pseudotyped retroviruses. This modification allows for a greatly improved efficiency of gene transfer by the recombinant viruses. Our recombinant viruses bearing the Ebola virus glycoproteins are particularly suited for gene therapy for diseases such as cystic fibrosis.