Deadly Ebola Virus May Mutate to Evade Drug Treatments

The deadly Ebola virus may be a lot more dangerous than we once thought. It seems as if genetic mutations called "escape variants" in Ebola block the ability of antibody-based treatments to ward of infection.

The Ebola virus has claimed the lives of over 11,000 people in West Africa since last year. It overruns the immune system, overwhelming the host's ability to fight off the infection. One strategy for treatment is based on the administration of a "cocktail" of antibodies that have the ability to neutralize the virus and allow the host to mount an effective immune response.

One of these cocktails, known as MB-003, has managed to help nonhuman primates infected with the virus. Now, a more advanced formulation, ZMapp, is currently in development and authorized for use in the West African Ebola outbreak response.

Now, though, it seems as if Ebola may get around the new treatment. Researchers examined nonhuman primates that were given MB-003, but still succumbed to the infection. The scientists found two clusters of changes in the viral genome that corresponded with the viral target sites of two of the cocktail's antibodies.

"The molecular analysis allowed us to see where the cocktails were inducing changes in the genome, and to link those changes to the treatment failure," said Jeffrey Kugelman, co-author of the new study, in a news release. "When this rescued virus was sequenced, we observed that the clusters of changes had progressed from affecting a small portion of the viral population to becoming mutations-permanent changes in the genome-without disrupting any major viral functions, including the ability to cause infection."

The new findings show that researchers will need to keep up to date when it comes to designing treatments for Ebola. In addition, they highlight the importance of selecting different target domains for each component of the therapeutic cocktail to minimize the potential for viral escape.

The findings are published in the journal Cell Reports.

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