Research reveals how Ebola virus blocks immune system

The Ebola virus, in the midst of its biggest outbreak on record, is a master at evading the body’s immune system. But researchers at Washington University School of Medicine in St. Louis and elsewhere have learned one way the virus dodges the body’s antiviral defenses, providing important insight that could lead to new therapies.

Research reveals how Ebola virus blocks immune system

The virus has infected about 1,800 people since March in four West African nations and killed more than half of them, according to the World Health Organization.

The researchers developed a detailed map of how an Ebola protein, VP24, binds to a host protein that takes signaling molecules in and out of the cell nucleus. Their map revealed that the viral protein takes away the host protein’s ability to carry an important immune signal into the nucleus.

This signal helps activate the immune system’s antiviral defenses, and blocking it is believed to contribute significantly to the virus’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 senior author Gaya Amarasinghe, PhD, 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.”

The results appear Aug. 13 in Cell Host & Microbe.

A National Institutes of Health (NIH) grant of up to $15 million, awarded March 1, is helping Amarasinghe and other researchers look for drugs to block VP24 and another Ebola protein, VP35. The group includes researchers at the Icahn School of Medicine at Mount Sinai, Washington University, the University of Texas Southwestern Medical Center, Howard University and Microbiotix Inc., a Massachussetts biopharmaceutical company.

Co-author Christopher Basler, PhD, professor of microbiology at Mount Sinai and the principal investigator of the consortium, was the first to show that VP24 and VP35 were important to the virus’s ability to keep the immune system at bay.

In an earlier paper, Amarasinghe, Basler and others revealed that VP35 blocks production of interferon, one of the main regulators of the innate immune system. This branch of the immune system specializes in fighting viruses.

“Interferon is critical to our ability to defend ourselves against viruses,” Basler said. “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.”

In the new study, Amarasinghe and Daisy Leung, PhD, assistant professor of pathology and immunology at Washington University, showed that 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,” Leung said. “But when VP24 is attached to some of these transporters, STAT1 can’t get into the nucleus.”

The researchers found that VP24’s 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.

Source: washington university


Nigeria to get Japanese drug for Ebola treatment

Nigeria will soon get a Japanese drug to treat Ebola, the country’s Health Minister Onyebuchi Chukwu said on Monday. The drug named Favipiravir and developed by a subsidiary of Fujifilm Holdings in Japan, could be delivered any time soon in Nigeria, Xinhua quoted Chukwu as telling reporters here.

Nigeria to get Japanese drug for Ebola treatment

Apart from the Japanese drug, the west African country had also applied for another anti-Ebola drug alongside two other vaccines, which have been positively identified by the local Treatment Research Group (TRG) in Nigeria.

“The TRG has been working hard to identify experimental drugs like Zmapp, and also make recommendations to government on further research on these drugs as well as vaccines for EVD treatment and prevention,” Chukwu said. The Nigerian minister said the drug was considered as it has strong anti-viral property against Ebola virus in-vitro and in-vivo.
“These and the fact that it is considered safe, having passed through phases one and two clinical trails makes it good candidate drug for use in emergency situation as the EVD,” he added.

Elaborating on the Ebola spread, Chukwu said total number of cases in Nigeria stands at 16, while 13 people have been treated at the isolation ward in the southwestern state of Lagos. So far, seven people have been discharged from the isolation facility.

He noted six people had died of Ebola so far in Africa’s most populous country, with five fatalities in Lagos and only one fatality recorded in the oil-rich city of Port Harcourt. More than 1,500 people have so far died of Ebola since the latest outbreak in West African countries began in March.

Source: one india


Ebola scare at Delhi airport, 3 Indians taken for test

Three Indians who arrived at the Delhi airport on Tuesday morning from Ebola-hit Liberia have been isolated and taken for medical examination. A total of 112 people will be arriving on Tuesday at Delhi and Mumbai airports from the African nation.

Ebola scare at Delhi airport, 3 Indians taken for test

Government has taken elaborate precautionary arrangements. “As part of the tentative plan, the aircraft will be first taken to a remote bay and all passengers will be screened at the step-ladder exit after the arrival of flights at the Chhatrapati Shivaji International Airport (CSIA),” Mumbai International Airport Limited (MIAL) said.

While the passengers without any symptoms will be cleared and shifted to the terminal for immigration and customs clearance, those coming from Liberia with symptoms suggestive of EVD will be shifted to designated hospital in ambulance from the bay, it said.

According to MIAL, Ethiopian Airline, Emirates, Etihad, Qatar, Jet and South African Airways are flying these passengers to Mumbai. Some of these passengers will first arrive in Delhi and then leave for Mumbai by domestic airlines flight, MIAL said.

Mial also said the baggage of the passengers needs to be kept separate by the concerned airline in their custody, adding disinfection of the flight will be carried out once all passengers would be deboarded.

Flights will be allowed to board the next batch of passengers only after thirty minutes of disinfection, it added.
Source: India Today