A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease
Abstract
Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV resulted in a single mutation in the region encoding the glycoprotein (GP). This is a region where mutations can have important consequences on outbreaks and human disease [S. Mahanty and M. Bray, Lancet Infect Dis 4:487–498, 2004, https://doi.org/10.1016/S1473-3099(04)01103-X ]. We thus investigated whether this mutation impacted disease by using a cynomolgus macaque model of MARV infection. Monkeys exposed to virus containing the mutation had better clinical outcomes than monkeys exposed to virus without the mutation. We also observed that a remarkably low number of MARV particles was sufficient to cause death. Our results could have a significant impact on how future studies are designed to model MARV disease and test vaccines and therapeutics.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 28, 2018
- Source ID
- 10.1128/msphere.00401-17
Entities
People
- Anthony Griffiths
- Jean L. Patterson
- Jenny Delgado
- Kendra J. Alfson
- Laura E. Avena
- Michael W. Beadles
- Ricardo Carrion Jr.
Organizations
- Texas Biomedical Research Institute
- United States Department of Defense
- University of Texas System