Q&A

S&T
Q. How does the Ebola virus immobilise our immune system?
A. Discovery of the protein that makes the Ebola virus so effective at evading the immune systemand
so deadlyis necessary to develop more effective treatments.
The Ebola virus, in the midst of its biggest outbreak on record, has infected thousands of people since
March 2014 in four West African nations and killed more than half of them, according to the World
Health Organization.
Researchers have developed a detailed map of how the protein, VP24, binds to a host protein that takes
signaling molecules in and out of the cell nucleus. The map reveals that the viral protein takes away the
host proteins ability to carry an important immune signal into the nucleus.
This signal helps activate the immune systems antiviral defenses, and blocking it is believed to
contribute significantly to the viruss deadliness.
Infection with Ebola obstructs an important arm in our immune system that is activated by molecules
called interferons .
VP24 and VP35 are important to the viruss ability to keep the immune system at bay.
VP35 blocks production of interferon, one of the main regulators of the innate immune system.
Interferon is critical to our ability to defend ourselves against viruses. 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.
VP24 tightly binds to a nuclear transporter, a protein that takes molecules into and out of the cell
nucleus. Among the molecules these transporters take into the nucleus is STAT1, an important
component of the interferon signaling pathway.
Normally STAT1 is transported into the nucleus and activates the genes for hundreds of proteins
involved in antiviral responses. But when VP24 is attached to some of these transporters, STAT1 cant
get into the nucleus.
One study shows that VP24s action specifically prevents STAT1 transport. Other proteins that travel in
and out of the cell nucleus and are important to viral replication likely are unaffected. The scientists
already have initiated efforts to look for small molecules that block VP35 and now are applying those
same approaches to VP24.
Researchers are looking for drugs to block VP24 and another Ebola protein, VP35.
Lik