Mount Sinai Scientists Discover How Marburg Virus Grows in Cells

Article

A protein that normally protects cells from environmental stresses has been shown to interact Marburg virus VP24, allowing the deadly Marburg virus to live longer and replicate better, according to a cell culture study led by scientists at the Icahn School of Medicine at Mount Sinai. The investigators say that deciphering the molecular details of how Marburg virus and the host protein interact may help in developing inhibitors of the virus. Results from the study are published online March 13 in the journal Cell Reports.

Infections with Marburg virus lead to death in as many as 90 percent of those infected. Once restricted to Africa, cases of the virus have been identified in travelers from Europe and the United States, making effective prevention and treatment a top biodefense priority.

“Marburg virus has been essentially untreatable,” says the study’s senior author, Christopher F. Basler, PhD, professor of microbiology at the Icahn School of Medicine at Mount Sinai. “Our study shows that Marburg virus VP24 interacts with the host protein Keap1.” Basler explains that Keap1 regulates the antioxidant response, normally protecting cells from harm. When the virus interacts with Keap1, Marburg virus-infected cells survive longer, facilitating virus growth.

The research builds on previous research in Basler’s lab. Studying Ebola virus, they found that Ebola virus VP24 protein blocks interferon, an important part of the host defense against virus detection. Unlike Ebola virus, a different host protein was shown to interact with Marburg virus.

“If we can develop inhibitors, the virus will die and replicate more slowly – that’s the hypothesis that we have now,” says Basler. Next, his laboratory hopes to pursue research and development of targeted therapies.

Megan Edwards, also from the Icahn School of Medicine at Mount Sinai, was the lead author of this research.

This work was supported by NIH grants AI059536 and AI081914 and DOD Defense Threat Reduction Agency grant HDTRA1-12-1-0051.

Source: Mount Sinai

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