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Chimpanzee: a type of ape that is smaller than a gorilla and that lives mostly in trees.
Immune system: all the cells, tissues, and organs involved in fighting infection or disease in the body... more
Mutation: a change in the lineup of DNA instructions. Sometimes, if the DNA changes, then the instructions for what to build will change, or mutate.
Replicate: to make a copy or to reproduce.
Reservoir (host): a host that carries a pathogen, often without showing negative signs of disease, and may be the source of future infections for humans.
RNA: an acid found in all living things that carries messages from DNA to the rest of the cell to be made into protein.
The virus enters your body through a bite you got while handling a monkey. It slips inside a host cell and hijacks the cell’s controls. The host cell suddenly begins making more and more viruses until the cell bursts open. Those new viruses then slip inside other cells, and the vicious cycle repeats.
More immune cells arrive to clean up the mess of dead cell parts. They try to clean up the viral infection as well, but the Ebola virus evades them. Eventually, the virus will infect most of the cells in your body, including the cells that make up your blood vessels. When these cells die, blood vessels become leaky. This causes internal bleeding, which can lead to multiple organ failure because the tissues in your body are not getting enough oxygen and nutrients. This is what leads to death in roughly 30 to 50% of patients infected with Ebola. Most patients start out with flu-like symptoms that worsen, and they die within the week.
How does the virus evade our immune systems so easily? Scientists compared the Ebola viruses involved in different outbreaks to learn how the virus evolves in the PLOS ONE article "New Perspectives on Ebola Virus Evolution."
The deadly Ebola virus contains a single strand of genetic material called RNA. Each gene in the strand serves as a blueprint to make proteins, which embed onto the surface of the membrane. One of these is the glycoprotein gene. This gene codes for two membrane proteins: the spike glycoprotein and the secreted glycoprotein.
Like all viruses, Ebola needs to hijack a host cell in order to survive and replicate. The spike glycoprotein, a protein with an attached carbohydrate, helps the virus enter and infect host cells. The secreted glycoprotein acts as a decoy: it lures the immune system’s attention away from the spike glycoprotein. The immune system starts producing antibodies to fight the secreted glycoprotein, while the spike glycoprotein continues to sneak the virus into cells. Thus, the Ebola virus keeps the immune system guessing while the infection grows stronger.
Since the mid-1970s, outbreaks of Ebola virus have erupted in human, chimpanzee, and gorilla populations in western African countries. However, there are long spans of time between outbreaks. During these lulls, the virus hides in reservoir species. Reservoirs are animals in which the Ebola virus can replicate enough to stay present, but not enough to make the animal sick. Scientists still do not know what the reservoir species for the Ebola virus are.
Since the discovery of Ebola, scientists have collected and stored information about glycoprotein genes from different virus outbreaks. They have noticed that not all glycoprotein genes are the same. How can this be?
When viruses replicate, they replicate and pass on copies of their genes to their “offspring.” During copying, mistakes can result in gene mutations. For example, imagine if you copy a tricky word such as “rhythm” a thousand times. Every so often, you will most likely make a spelling mistake and “mutate” the original word by adding, deleting, or switching one or two letters.
Differences between the glycoprotein genes most likely come from these random mutations. Mutations can change the amino acids that make up the glycoprotein, which leads to a change in the protein’s shape. For proteins, the shape determines what it can do. The spike glycoprotein is broken down into parts. One part is disordered, or unstructured, because its chemical composition cannot maintain structure. The other part is structured. Scientists compared the evolution of the glycoproteins to understand how these shapes may change over time and affect the survival of the virus.
Factors in the virus’ environment, such has the host immune system, will determine if the mutated gene is beneficial or not. If a mutation helps the Ebola virus survive longer and replicate faster, then the virus has experienced positive selection. If the mutation weakens the virus and the virus cannot replicate, then the virus has experienced purifying selection. Usually, with purifying selection, the mutated version of the gene dies out over time. Most mutations, however, do not affect the ability of the virus to survive and replicate. In these cases, we acknowledge that the gene has still changed over time due to genetic drift.
Scientists compared the glycoprotein genes from Ebola viruses collected from different outbreaks. Researchers first downloaded the genetic information from online databases. They then constructed a phylogenetic tree to track how different parts of the glycoprotein genes had changed over time. By tracking these changes, scientists determined which parts of the glycoprotein genes had experienced positive or purifying selection, or have collected mutations that do not affect its survival.
Constructing the phylogenetic tree of different Ebola virus glycoprotein genes led to four main conclusions:
Now that we know which parts of glycoproteins are most important for virus success, we need to understand how other species can affect the evolution of those proteins. Future works should focus on finding the reservoir species of the Ebola virus. By identifying the reservoir species, scientists may be able to understand how the virus changes between outbreaks and how it jumps from a reservoir to humans. Until then, it will be very difficult to predict and prevent the next Ebola virus outbreak.
EvMed Edits are sponsored by ASU's Center for Evolution and Medicine.
Additional images via Wikimedia Commons. Colored ebola virus particles by Thomas W. Geisbert; black and white ebola virus by the CDC.
Sisi Gao. (2017, July 05). Tracking Ebola through Time. ASU - Ask A Biologist. Retrieved March 24, 2019 from https://askabiologist.asu.edu/evmed-edit/ebola-evolution
Sisi Gao. "Tracking Ebola through Time". ASU - Ask A Biologist. 05 July, 2017. https://askabiologist.asu.edu/evmed-edit/ebola-evolution
Sisi Gao. "Tracking Ebola through Time". ASU - Ask A Biologist. 05 Jul 2017. ASU - Ask A Biologist, Web. 24 Mar 2019. https://askabiologist.asu.edu/evmed-edit/ebola-evolution
The Ebola virus seems fairly simple - a single strand of RNA - but it sneaks into cells, such as those that make up the immune system, and starts replicating. Once the infection spreads, the Ebola virus causes an often-fatal disease.