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What does Ebola actually do?
What does Ebola actually do?
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.
What ultimately kills Ebola patients?
Damage to blood vessels leads to a drop in blood pressure, and patients die from shock and multiple organ failure.
Why do some people survive infection?
Patients fare better with supportive care, including oral or
intravenous rehydration that can buy time for the body to fight off
infection. But studies on blood samples from patients during the 2000
outbreak of a different Ebola strain in Uganda have also identified
genes and other markers that seem to be predictive of survival. Patients
who recovered had higher levels of activated T cells in their blood and
had certain variants of a gene that codes for surface proteins that white blood cells use to communicate. Earlier this year, researchers found a new association between survival and levels of sCD40L,
a protein produced by platelets that could be part of the body’s
attempt to repair damaged blood vessels. The authors note that markers
like sCD40L could suggest new therapies that augment the repair
mechanisms most important for survival.
*Correction, 15 August, 1:51 p.m.: This article has been corrected to note that nitric oxide, not nitrous oxide, damages blood vessels.
*The Ebola Files: Given the current Ebola outbreak, unprecedented
in terms of number of people killed and rapid geographic spread, Science and Science Translational Medicine have made a collection of research and news articles on the viral disease freely available to researchers and the general public.
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13 August 2014 3:00 pm
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