By: Kelly Servick –
Behind the unprecedented Ebola outbreak in West Africa lies a species with an incredible power to overtake its host. Zaire ebolavirus and the family of filoviruses to which it belongs owe their virulence to mechanisms that first disarm the immune response and then dismantle the vascular system. The virus progresses so quickly that researchers have struggled to tease out the precise sequence of events, particularly in the midst of an outbreak. Much is still unknown, including the role of some of the seven proteins that the virus’s RNA makes by hijacking the machinery of host cells and the type of immune response necessary to defeat the virus before it spreads throughout the body. But researchers can test how the live virus attacks different cells in culture and can observe the disease’s progression in nonhuman primates—a nearly identical model to humans.
Here are some of the basic things we understand about how Ebola and humans interact.
What does Ebola do to the immune system?
Once the virus enters the body, it targets several types of immune cells that represent the first line of defense against invasion. It infects dendritic cells, which normally display signals of an infection on their surfaces to activate T lymphocytes—the white blood cells that could destroy other infected cells before the virus replicates further. With defective dendritic cells failing to give the right signal, the T cells don’t respond to infection, and neither do the antibodies that depend on them for activation. The virus can start replicating immediately and very quickly.
Ebola, like many viruses, works in part by inhibiting interferon—a type of molecule that cells use to hinder further viral reproduction. In a new study published today in Cell Host & Microbe, researchers found that one of Ebola’s proteins, called VP24, binds to and blocks a transport protein on the surface of immune cells that plays an important role in the interferon pathway.
Curiously, lymphocytes themselves don’t become infected with the virus, but a series of other factors—a lack of stimulation from some cells and toxic signals from others—prevent these primary immune cells from putting up a fight.
How does Ebola cause hemorrhaging?
As the virus travels in the blood to new sites, other immune cells called macrophages eat it up. Once infected, they release proteins that trigger coagulation, forming small clots throughout the blood vessels and reducing blood supply to organs. They also produce other inflammatory signaling proteins and nitric oxide, which damage the lining of blood vessels, causing them to leak. Although this damage is one of the main symptoms of infection, not all patients exhibit external hemorrhaging—bleeding from the eyes, nose, or other orifices.
Does the virus target certain organs?
Ebola triggers a system-wide inflammation and fever and can also damage many types of tissues in the body, either by prompting immune cells such as macrophages to release inflammatory molecules or by direct damage: invading the cells and consuming them from within. But the consequences are especially profound in the liver, where Ebola wipes out cells required to produce coagulation proteins and other important components of plasma. Damaged cells in the gastrointestinal tract lead to diarrhea that often puts patients at risk of dehydration. And in the adrenal gland, the virus cripples the cells that make steroids to regulate blood pressure and causes circulatory failure that can starve organs of oxygen.
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