A magazine for friends of the Warren Alpert Medical School of Brown University.

Ask the Expert: Ebola

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Ebola viruses are masters of their attack.

Why is Ebola so dangerous?
As the death toll soars in the massive Ebola outbreak, Brown’s science news officer, David Orenstein, asks infectious disease researcher Ian Michelow, MD, assistant professor of pediatrics, about the virus’s biology and what makes it so pernicious.

The implicated virus is related to Zaire ebolavirus, which is the most virulent of the five known Ebola virus species. Like many other pathogens, Ebola viruses have developed and perfected strategies to evade, suppress, or manipulate the host’s immune response. To subvert humans’ armamentarium, the enveloped Ebola viruses must deposit their genetic material within a cell to survive and propagate without interference. They hijack macrophages and dendritic cells to spread infection to nearly every organ of the body, especially the liver, spleen, and lymph nodes.

Ebola viruses strike rapidly to immobilize humans’ early innate immune responses. The viruses ensconce themselves in a cloak of glycans in an attempt to shield themselves from neutralizing antibodies and to direct the production of antibodies to highly variable or dispensable regions on the viral surface. Ebola viruses also produce free glycoproteins that are thought to cause production of nonneutralizing antibodies, thereby preventing effective neutralization of the virus.

In a desperate attempt to counter the viruses, human cells produce large amounts of signaling proteins called cytokines and chemokines, but the response is highly deregulated because the virus disrupts the immune system. The consequent “cytokine storm” leads to systemic inflammatory response syndrome and the death or dysfunction of many immune system cells. As the disease progresses, it leads to problems such as clots and extensive tissue death, hemorrhage in a third of patients, and possible multi-organ failure and death within seven to 10 days in up to 90 percent of cases caused by the most virulent strains.

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