A newly developed mouse model suggests that genetic factors are behind the mild-to-deadly range of reactions to the Ebola virus. In the study, recently published in 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. The research was conducted in a highly secure biocontainment safety level 4 laboratory in Hamilton, MT, in full compliance with federal, state, and local safety and biosecurity regulations.
The scientists examined mice that they infected with a mouse form of the same species of Ebola virus that caused the 2014 West Africa outbreak. All the mice lost weight in the first few days after infection. Nineteen percent were unfazed; they not only survived but fully regained their lost weight within two weeks. They had no gross pathological evidence of disease, and their livers looked normal. Eleven percent were partially resistant, and < half of these died. Seventy percent of the mice had a > 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. 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 researchers 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. They believe this mouse model can be implemented to find genetic markers, conduct meticulous studies on how symptoms originate and take hold, and evaluate drugs and that have broad spectrum antiviral activities against all Zaire ebolaviruses. Read the study.
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