A protein that interacts with Marburg virus VP24 and allows the deadly Marburg virus to live longer and replicate better is the one that normally protects cells from environmental stress, find researchers in 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 peer-reviewed journal Cell Reports.
Infections with Marburg virus lead to death in as many as 90% 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," said 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." Dr. Basler explained 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 Dr. 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," said Dr. 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.
About the Mount Sinai Health System:
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services-from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.