Viral takeover: how viruses take advantage of infected cells

It’s that time of year when everyone seems to be catching some kind of virus. While you might be familiar with a virus’s potential to make you feel miserable, have you ever wondered how viruses work to cause illness? A virus is much like a robber in a factory. A viral “robber” has both a strategy to get into the factory and the ability to use the machines to make what it wants. Similarly, when a virus gets access to the cells of your body it is able to hijack the machinery that your cell would normally use to replicate its genetic material and make its own proteins. The virus can use your cells to make more copies of itself and spread from cell to cell. How does your cell get tricked into making more virus? One lab at K-State has found a way that one sneaky virus accomplishes this. The culprit: vaccinia virus.

Vaccinia virus comes from a family of viruses called poxviruses. You might know its more famous cousin, the variola virus, which causes the deadly infectious disease smallpox. When the vaccinia virus enters a cell, it must go through several steps using the cell’s machinery to make new viruses. The viral DNA contains the master plans that get copied into messenger RNA, the blueprints for protein production. When researchers looked at the messenger RNA of this virus they found something very odd. They found that in later stages of infection, the viral “protein blueprints” have an added unusual repeating sequence of information.

Comparison uninfected and infected cells
This image shows two different groups of HFF cells, a type of human cell used to study viral infections in the lab. Those on the left are regular, uninfected HFF cells, while those on the right have been infected with vaccinia virus. Researchers can compare different traits between the infected and uninfected cells to study how viral infections work. Photo credit: Pragyesh Dhungel

Curious biology graduate student Pragyesh Dhungel decided to take up the case using a clever and luminous approach. Pragyesh and his colleagues infected cells with the virus and then fed these cells the repeating sequence attached to the blueprint for a protein called firefly luciferase. While you may have never heard the name of this protein you probably have enjoyed watching it dance around the sky on summer evenings. Luciferase is the protein responsible for the light produced by fireflies! When the blueprint for this protein is given to a cell, the cell will use its machinery to make the protein. The more luciferase that is produced, the more the cell will light up, and this light can be used as a way to measure how much protein is being made (other K-State researchers use a similar technique with jellyfish proteins). Pragyesh found that when the repeating sequence mentioned earlier is added to the blueprint for luciferase, it caused the cell to make more firefly luciferase, acting as a substitute for a true viral protein, instead of the cell’s own proteins. By adding this repeating sequence to the blueprints for its own proteins, the virus causes the hijacked cell to prioritize making viral proteins. This is just one way that the clever vaccinia virus can outwit an unsuspecting cell.

Graduate student Pragyesh Dhungel
Pragyesh Dhungel conducting research on vaccinia virus. Photo credit: K-State Today

While in everyday life we tend to think of viruses as the reason for our runny nose or cough, there is so much going on behind the scenes. This exciting research is important in learning about how virus “robbers” are able to take over our factories’ machinery. The more that we know about how viruses take over our cells the better we can develop treatments to prevent such a takeover.

This post is a highlight of a research article Pragyesh and colleagues recently published in PLOS Pathogens.

IMG_1755This post was written by Alexis Carpenter, a first year biology Ph.D. student. She studies how viruses are able to escape from the midgut of mosquitoes and potentially be transmitted to humans.

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