The Ebola outbreak in West Africa has brought a lot of attention to the deadly virus. According to the World Health Organization, up to 90% of those infected with Ebola die from the virus. Now, researchers publishing August 13 in the Cell Press journal Cell Host & Microbe reveal how Ebola blocks and disables the body's natural immune response. Understanding how Ebola disarms immune defenses will be crucial in the development of new treatments for the disease.
Dr. Gaya Amarasinghe and colleagues from Washington University School of Medicine along with collaborators from the Icahn School of Medicine at Mount Sinai and UT Southwestern Medical Center at Dallas show how the Ebola protein VP24 disrupts the cell's innate immune response, a crucial early step on the virus's path to causing deadly disease.
"We've known for a long time that infection with Ebola obstructs an important immune compound called interferon," said Amarasinghe. "Now we know how Ebola does this, and that can guide the development of new treatments."
According to the researchers, VP24 works by preventing the transcription factor STAT1, which carries interferon's antiviral message, from entering the nucleus and initiating an immune response. As part of a rapid immune response, the cell allows STAT1 an "emergency access lane" to the nucleus. Rather than block all nuclear transfer, however, VP24 focuses on blocking STAT1's "emergency access lane."
"Normally interferon causes STAT1 to enter the cell nucleus, where it activates the genes for hundreds of proteins involved in antiviral responses," Dr. Daisy Leung from Washington University School of Medicine said. "But when VP24 is attached to STAT1, it can't get into the nucleus."
"One of the key reasons that Ebola virus is so deadly is because it disrupts the body's immune response to the infection," said Dr. Chris Basler of the Icahn School of Medicine at Mount Sinai. "Figuring out how VP24 promotes this disruption will suggest new ways to defeat the virus."
These findings come at a critical time for Ebola research. If researchers carry out further study of VP24, it can open the door to new possibilities for disarming the protein's effect on immune response.
Cell Host & Microbe, Xu et al.: "Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1."