How Ebola blocks immune system

American researchers have developed a detailed map of the Ebola protein VP24, which has revealed how the virus dodges the body’s antiviral defences – an insight which could lead to new therapies. VP24 binds to a host protein that takes signalling molecules in and out of the cell nucleus, say researchers from Washington University in St Louis. The map reveals the viral protein removes the host protein’s ability to carry an important immune signal to the nucleus. This signal helps to activate antiviral defences, and blocking it is believed to contribute significantly to Ebola’s deadliness. “We’ve known for a long time that infection with Ebola obstructs an important arm in our immune system that is activated by molecules called interferons,” said Gaya Amarasinghe, assistant professor of pathology and immunology at the School of Medicine. “Now that our map of the combined structure of these two proteins has revealed one critical way Ebola does this, the information it provides will guide the development of new treatments.” Published in Cell Host & Microbe, the research shows that VP24 bind tightly to a nuclear transporter which takes molecules in and out of the cell – among these is STAT1, an important part of the interferon signalling pathway. “Normally STAT1 is transported into the nucleus and activates the genes for hundreds of proteins involved in antiviral responses,” said Daisy Leung, assistant professor of pathology and immunology. “But when VP24 is attached to some of these transporters, STAT1 can’t get into the nucleus.” The researchers are now looking for drugs that can block VP24 and VP35, another Ebola protein which blocks the production of interferon, one of the main regulators of the innate immune system. “Interferon is critical to our ability to defend ourselves against viruses,” said Christopher Basler, professor of microbiology at Mount Sinai who is also involved in this work. “It makes a variety of responses to viral infection possible, including the self-destruction of infected cells and the blockage of supplies necessary for viral reproduction.” Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1 Useful links: The World Health Organization Global Alert and Response: Ebola Virus disease Ebola factsheet: (source http://www.who.int/mediacentre/factsheets/fs103/en/)

• The Ebola virus causes Ebola virus disease (EVD; formerly known as Ebola haemorrhagic fever) in humans.
• EVD outbreaks have a case fatality rate of up to 90%.
• Ebola first appeared in 1976 in 2 simultaneous outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo. The latter was in a village situated near the Ebola River, from which the disease takes its name.
• EVD outbreaks occur primarily in remote villages in Central and West Africa, near tropical rainforests.
• Genus Ebolavirus is 1 of 3 members of the Filoviridae family (filovirus), along with genus Marburgvirus and genus Cuevavirus. Genus Ebolavirus comprises 5 distinct species.
• The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.
• Fruit bats of the Pteropodidae family are considered to be the natural host of the Ebola virus.
• No specific treatment or vaccine is available for use in people or animals.