Unlocking the mystery of varied immune response to Ebola
10/02/2015 // News // Text: Rod Hise // Photo: George Shuklin

Study results: mouse model might provide foundation for therapies, vaccines.

It started with two-year-old Emile Ouamouno in the remote Guinean village of Meliandou in West Africa. Emile died just days after first showing signs of the infection that would ravage his young body—a spiked fever and, quickly after, the telltale black stool and vomit caused by internal bleeding. Emile was patient zero in the latest outbreak of the Ebola virus that began in late 2013. Until the disease struck Emile, this species of Ebola virus had never been seen in West Africa.

But as pathogenic as the Ebola virus is, not all who are infected with it will bleed severely. Some of those infected with Ebola don’t get sick at all. The World Health Organization reports that more than 22,000 cases of Ebola infection have been recorded in the six-country region in West Africa where the most recent outbreak has occurred. More than 9,000 people have died from it.

A team at the University of Washington in Seattle has significantly advanced the understanding of what causes these differences in immune response. The scientists, led by Angela Rasmussen, Ph.D., found that variations in the immune responses in the 47 mouse lines they studied were linked to the genetic makeup of the mice. The study results were published recently in the journal Science and hailed as a seminal work by thought leaders in the field.

Using QIAGEN’s RNA isolation and transcription products, and the company’s innovative Ingenuity Pathway Analysis and CLC Genomics Workbench bioinformatics tools, Dr. Rasmussen and her team found that two genes in particular played a key role in determining whether the mice became sick, died or didn’t become sick at all. Low activity of the Tie1 and Tek genes were associated with lower resistance to Ebola infection, the study showed. The research was conducted in a highly secure, biosafety-level 4 laboratory in Montana using a mouse-adapted Ebola virus related to the one that caused the West African outbreak.

Nineteen percent of the mice were not severely affected by Ebola infection. Another 11 percent of the mice in the study were partially resistant to Ebola; only half of them died.  The balance of the mice, or 70 percent, reacted severely to the virus and more than half of them, many from the classic symptoms of fatal Ebola infection disease in humans, including slow-clotting blood, internal bleeding, and swollen and discolored internal organs. The differing severities of illness and their percentages in the study’s mouse population are similar to the patterns seen in humans in West Africa, the researchers said.

“We found that genetics plays a significant part in how a mouse responds to an Ebola infection,” Dr. Rasmussen said. “This is an important finding on its own, but we also can make an inference from our study that genetics probably plays an important role in how humans respond to the virus, too. We are looking forward to continuing our research to evaluate that connection in more depth.”

Dr. Rasmussen and her team now hope that their findings can be used to find potential therapies for Ebola infection and vaccines against it. Mouse models that reproduce the full range of Ebola virus disease symptoms haven’t been available until now. Access to the new models developed by Dr. Rasmussen and her colleagues should accelerate efforts to identify new therapies and vaccines.

For more information, you can download the complete case study (PDF) from the QIAGEN bioinformatics website.


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