Genetic factors behind surviving or dying from Ebola shown in mouse study

October 30, 2014

A newly developed mouse model suggests that genetic factors are behind the mild-to-deadly range of reactions to the Ebola virus.

People exposed to Ebola vary in how the virus affects them. Some completely resist the disease, others suffer moderate to severe illness and recover, while those who are most susceptible succumb to bleeding, organ failure and shock.

In earlier studies of populations of people who have contracted Ebola, these differences are not related to any specific changes in the Ebola virus itself that made it more or less dangerous; instead, the body's attempts to fight infection seems to determine disease severity.

In the Oct. 30 edition of Science, scientists describe strains of laboratory mice bred to test the role of an individual's genetic makeup in the course of Ebola disease. Systems biologists and virologists Angela Rasmussen and Michael Katze from the Katze Laboratory at the University of Washington Department of Microbiology led the study in collaboration with the National Institutes of Health's Rocky Mountain Laboratories in Montana and University of North Carolina at Chapel Hill.

Research on Ebola prevention and treatment has been hindered by the lack of a mouse model that replicates the main characteristics of human Ebola hemorrhagic fever. The researchers had originally obtained this genetically diverse group of inbred laboratory mice to study locations on mouse genomes associated with influenza severity.

The research was conducted in a highly secure, state-of-the-art biocontainment safety level 4 laboratory in Hamilton, Mont. The scientists examined mice that they infected with a mouse form of the same species of Ebola virus causing the 2014 West Africa outbreak. The study was done in full compliance with federal, state, and local safety and biosecurity regulations. This type of virus has been used several times before in research studies. Nothing was done to change the virus.

Interestingly, conventional laboratory mice previously infected with this virus died, but did not develop symptoms of Ebola hemorrhagic fever.

In the present study, all the mice lost weight in the first few days after infection. Nineteen percent of the mice were unfazed. They not only survived, but also fully regained their lost weight within two weeks. They had no gross pathological evidence of disease. Their livers looked normal.

Eleven percent were partially resistant and less than half of these died. Seventy percent of the mice had a greater than 50 percent mortality. Nineteen percent of this last group had liver inflammation without classic symptoms of Ebola, and thirty-four percent had blood that took too long to clot, a hallmark of fatal Ebola hemorrhagic fever in humans. Those mice also had internal bleeding, swollen spleens and changes in liver color and texture.

The scientists correlated disease outcomes and variations in mortality rates to specific genetic lines of mice.

"The frequency of different manifestations of the disease across the lines of these mice screened so far are similar in variety and proportion to the spectrum of clinical disease observed in the 2014 West African outbreak," Rasmussen said.

While acknowledging that recent Ebola survivors may have had immunity to this or a related virus that saved them during this epidemic, Katze said, "Our data suggest that genetic factors play a significant role in disease outcome."

In general, when virus infection frenzied the genes involved in promoting blood vessel inflammation and cell death, serious or fatal disease followed. On the other hand, survivors experienced more activity in genes that order blood vessel repair and the production of infection-fighting white blood cells.

The scientists note that certain specialized types of cells in the liver could also have limited virus reproduction and put a damper on systemic inflammation and blood clotting problems in resistant mice. Susceptible mice had widespread liver infection, which may explain why they had more virus in their bodies and poorly regulated blood coagulation. The researchers also noticed that spleens in the resistant and susceptible mice took alternate routes to try to ward off infection.

"We hope that medical researchers will be able to rapidly apply these findings to candidate therapeutics and vaccines," Katze said. They believe this mouse model can be promptly implemented to find genetic markers, conduct meticulous studies on how symptoms originate and take hold, and evaluate drugs and that have broad spectrum anti-viral activities against all Zaire ebolaviruses, including the one responsible for the current West African epidemic.
-end-


University of Washington Health Sciences/UW Medicine

Related Ebola Articles from Brightsurf:

Targeting the shell of the Ebola virus
As the world grapples with COVID-19, the Ebola virus is again raging.

Why doesn't Ebola cause disease in bats, as it does in people?
A new study by researchers from The University of Texas Medical Branch at Galveston uncovered new information on why the Ebola virus can live within bats without causing them harm, while the same virus wreaks deadly havoc to people.

Ebola transmission risks would be taken more seriously with ground-up interventions
A study led by the University of Kent's Durrell Institute of Conservation and Ecology (DICE) has found significant differences in disease risk perception and channels of information about Ebola virus disease (EVD) in rural areas and urban centres of Guinea, West Africa.

US inroads to better Ebola vaccine
As the world focuses on finding a COVID-19 vaccine, research continues on other potentially catastrophic pandemic diseases, including Ebola and Marburg viruses.

Ebola antibodies at work
Scientists in Israel and Germany show, on the molecular level, how an experimental vaccine offers long-term protection against the disease.

Half of Ebola outbreaks undetected
An estimated half of Ebola virus disease outbreaks have gone undetected since it was discovered in 1976, according to research published in PLOS Neglected Tropical Diseases.

Protecting those on the frontline from Ebola
Online training developed at the Medical University of South Carolina (MUSC) increased the knowledge of health care workers about effective prevention of Ebola up to 19 percent and reduced critical errors to 2.3 percent in a small MUSC cohort.

Another piece of Ebola virus puzzle identified
A team of researchers have discovered the interaction between an Ebola virus protein and a protein in human cells that may be an important key to unlocking the pathway of replication of the killer disease in human hosts.

How the human immune system protects against Ebola
'The current approach for treatment of filovirus infections with antibody cocktails tested in animal models utilizes the principle of targeting of non-overlapping epitopes.

How to slow down Ebola
The phylogenetic tree of the 2013-2016 Ebola epidemic doesn't just tell us how the Ebola virus was able to evolve: it also reveals which events and preventive measures accelerated or slowed down its spread.

Read More: Ebola News and Ebola Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.