Ebola Survival Genetic?
An Ebola victim’s genetic make-up may be the deciding factor when it comes to the fatality of the Ebola virus, according to a study published in the October 30 edition of Science. The study, based on research conducted at the Rocky Mountain Laboratories level-four safety laboratory in Hamilton, MT, demonstrated that mice infected with the Ebola virus react differently to the infection on the basis of known genetic anomalies bred into the mice by researchers. Michael Katze, senior author of the study, says that the data suggests genetic factors at play in the severity of the disease and the patient outcome. Katz believes this information will be useful for the medical researchers who can apply these findings to candidate vaccines for a range of genetic factors.
The study was the result of a collaboration between three research centers, including the University of Washington, Seattle, the University of North Carolina and the National Institutes of Health (NIH). The researchers built their experiments on the basis of previous information garnered from laboratory studies on Ebola, and the understanding that the virus can cause a number of different reactions dependent on how the host receives it.
In some cases, the virus is rejected, in others there is anything from a mild reaction to organ failure and death. The nature of such multifarious behavior was something that the researchers, working with animal models, wanted to explore. Using a genetically diverse selection of mice called the Collaborative Cross resource, they bred strains of the infection that mimicked the underlying characteristics of the Ebola virus as expressed in humans.
Classically bred mice, which are not as genetically diverse as the Collaborative Cross mice variety, will die when infected with this strain of Ebola, but they will not suffer symptoms similar to that of hemorrhagic disease as seen in humans. The Collaborative Cross mice, with their greater genetic diversity, react to the virus in a manner comparable to humans.
This mouse-version of the infection that has caused the deaths of almost 5,000 people in West Africa this year, has been used to study the differences in disease outcome. Initially, it was observed that 100 percent of the mice infected with Ebola experienced weight loss. Nineteen percent however, were not severely affected. They regained the weight that they had lost and suffered no further symptoms. Eleven percent of the infected rodents demonstrated a partial resistance to the disease. Of this group, half died soon after being infected.
The remaining 70 percent showed severe reactions such as liver inflammation, bleeding spleens, and problems with blood clotting. These symptoms are similar to those seen in human patients. The researchers then studied the genetic make-up of the mice and looked for similarities between the groups.
Specific gene patterns were shown to underlie the severity of the reaction that the mice had to the Ebola virus. In the majority of cases, the virus activated genes involved in promoting cell death and inflammation of blood vessels. This pattern was true for the mice that suffered and died.
The mice that survived however, had a different reaction. In these mice, the virus activated genes which had a beneficial action on blood vessels and infection-fighting immune system cells.
There were also differences observed in the way that the spleen and liver reacted to the infection. In the mice that seemed resistant to the disease, the researchers noted that virus replication may have been limited by specialized liver cells. These cells lessened the severity of the inflammation and reduced the damage to the process of blood clotting.
Dr. Angela Rasmussen, from the microbiology and systems biology lab at the University of Washington, and co-author of the study, explained that the symptom pattern observed in the mouse population that the researchers studied was similar to that being seen in the human population in West Africa. She believes that there is a genetic component which determines the chances of survival that patients have.
Dr. Katze, who also heads the laboratory at the University of Washington, has said that it is possible there are other reasons that may explain the immunity as demonstrated in some of the people who have survived contracting the Ebola virus. This study however, provides data that suggests the outcome may be at least somewhat dependent on the genetic make-up of the host.
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