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Mount Sinai researchers discovered the intricate cellular mechanisms of Ebola virus. This could help to explain the severe effects on people and provide potential treatment or prevention. The team published a study in mBio that showed how VP24, a protein from the Ebola virus interacts with the double-layered cell membrane (known as the nucleus) and causes significant damage to cells. This results in virus replication and propagation.
The Ebola virus first appeared in 1976 in Africa. It has caused a series of outbreaks, the worst being in 2014-2016 in West Africa. There is a 50% mortality rate. This virus causes severe hemorhagic fever and is spread from wild animals to humans by human-to-human transmission.
The Ebola virus is extremely skilled at dodging the body’s immune defenses, and in our study, we characterize an important way in which that evasion occurs through disruption of the nuclear envelope, mediated by the VP24 protein. That disruption is quite dramatic and replicates rare, genetic diseases known as laminopathies, which can result in severe muscular, cardiovascular, and neuronal complications.”
Adolfo García-Sastre, Ph.D., Study Co-Senior Author, Professor and Director , Microbiology, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai
The laboratory work of the researchers, which was conducted mainly with research partners from CIMUS in Spain and Bernhard Nocht Institute for Tropical Medicine Hamburg, Germany, revealed the cellular membrane components that interact to VP24, causing nuclear membrane disruption. These components include emerin, the inner membrane constituents lamin C/C and lamin D. The VP24 protein reduces the interaction between lamin A/C, emerin, and compromises the integrity of nuclear membrane. This results in leakage and loss of function by body’s disease-fighting cell.
Researchers also found that VP24 interferes with signaling pathways that activate the immune system’s defenses from viral invaders such as Ebola. This has a biological consequence that is more detrimental to the normal physiology and function of cells, as well as antiviral immunity.
“We believe that our discovery of Ebola’s novel activities and the severe damage it does to infected cells will encourage further research into ways to prevent and treat deadly viruses from spreading,” said Dr. Garcia-Sastre. Garcia-Sastre has spent 25 years studying the molecular biology and genetics of rare and common viruses. In fact, this research will hopefully reveal more details about how viruses such as Ebola enter the body and provide ways to avoid it.
The Mount Sinai Hospital / Mount Sinai School of Medicine
Vidal, S., et al. (2021) Expression of the Ebola Virus VP24 Protein Compromises the Integrity of the Nuclear Envelope and Induces a Laminopathy-Like Cellular Phenotype. mBio. doi.org/10.1128/mBio.00972-21.