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Mechanisms behind Ebola Virus Spread Revealed

The Ebola Virus Disease (EVD) is a rare and deadly disease in people and nonhuman primates. The viruses that cause EVD are located mainly in sub-Saharan Africa. People can get EVD through direct contact with an infected animal (bat or nonhuman primate) or a sick or dead person infected with Ebola virus. The virus is extremely skilled at escaping the immune system’s defenses. However, new hope comes from a study by Mount Sinai researchers, who report they have uncovered the complex cellular mechanisms of Ebola virus. Their research may help to identify potential pathways to treatment and prevention.

The findings are published in the journal mBio, “Expression of the Ebola Virus VP24 Protein Compromises the Integrity of the Nuclear Envelope and Induces a Laminopathy-Like Cellular Phenotype.”

“Ebola virus (EBOV) VP24 protein is a nucleocapsid-associated protein that inhibits interferon (IFN) gene expression and counteracts the IFN-mediated antiviral response, preventing nuclear import of signal transducer and activator of transcription 1 (STAT1),” wrote the researchers. “Proteomic studies to identify additional EBOV VP24 partners have pointed to the nuclear membrane component emerin as a potential element of the VP24 cellular interactome. Here, we have further studied this interaction and its impact on cell biology. We demonstrate that VP24 interacts with emerin but also with other components of the inner nuclear membrane, such as lamin A/C and lamin B.” The team reported “how a protein of the Ebola virus, VP24, interacts with the double-layered membrane of the cell nucleus (known as the nuclear envelope), leading to significant damage to cells along with virus replication and the propagation of disease.”

“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,” said co-senior author Adolfo García-Sastre, PhD, professor of microbiology, and director of the Global Health and Emerging Pathogens Institute of the Icahn School of Medicine at Mount Sinai. “That disruption is quite dramatic and replicates rare, genetic diseases known as laminopathies, which can result in severe muscular, cardiovascular, and neuronal complications.”

The researchers collaborated with research partners from CIMUS at the Universidad de Santiago de Compostela in Spain, and the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany. Together, they identified the cellular membrane components that interact with VP24 to prompt nuclear membrane disruption.

The researchers demonstrated that VP24 disrupts signaling pathways that are meant to activate the immune system’s defenses against viruses.

“We believe our discovery of the novel activities of the Ebola VP24 protein and the severe damage it causes to infected cells will help to promote further research into effective ways to treat and prevent the spread of deadly viruses, perhaps through a new inhibitor,” added García-Sastre. “Indeed, that research will hopefully identify even more precisely the molecular mechanisms by which viruses like Ebola invade the body and find ways to cleverly avoid its immune defenses.”

The post Mechanisms behind Ebola Virus Spread Revealed appeared first on GEN – Genetic Engineering and Biotechnology News.

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