Yellow fever is one of those diseases that you really want to avoid contracting. But for 200,000 people every year, they don’t receive that option.

A Yellow Condition

The yellow fever virus is the originating name for its parent genus of Flaviviruses, where the yellow of its name in Latin (Flavus) colors all the rest of its cousin viruses. They are similarly horrible in their approach from symptoms of encephalitis to jaundice.

The direct cousins to the yellow fever virus also hitch a ride in the same host, the bane of many a country and especially South America as of late, the Aedes aegypti mosquito. As you can see from its relatives of dengue fever and Zika, yellow fever is in currently prestigious company, even though it is the original recognized disease in its family.

Protection From Disease

Luckily for those wishing to avoid suffering from the disease, there already exists a vaccine that is highly effective at granting a boost to the immune system against yellow fever. It is a live, attenuated version of the virus, as no version using dead proteins were found to be effective enough.

Instead, the attenuated version was made by changing the RNA genome expression by 1% from the actual virus, which is enough of a change to completely reduce the virulence of the virus. Named YFV-17D, it is still almost exact enough to the actual yellow fever virus that the immune system can properly respond and add its profile into the memory T-cell database.

As with all live vaccines, however, there is a small risk. In this case, it is due to the 1 in 300,000 cases where they have a genetic profile that negatively matches with the attenuated virus, enhancing virulent effects. Hopefully better genetic sequencing will allow these cases to be found beforehand and alternative methods created.

Understanding The Flow

On that topic, researchers at Princeton University have been investigating techniques that are capable of tracking how yellow fever replicates in human cells. They took a prior existing RNA assay tool called PrimeFlow that can detect and amplify the signals of RNA inside a cell. The scientists then took the technique and applied it to tracking the particles of yellow fever virus within immune cells.

Applying this to test mice, they were able to discover a special feature about the virus. Mice are generally immune to yellow fever, whether from the actual virus or the attenuated one. But when the transcription factor STAT1 was genetically disrupted in the mice cells, which is a part of the immune system’s signaling method to stop viral infections, they become susceptible to infection.

This result implies that it is the antiviral signaling system in mice that confers their immunity. Their immune system is able to quickly and accurately take out the virus before it can take hold. Additionally, there appear to be other species differences between humans and mice that make the virus less capable of infecting the latter.

Modifying Our Methods

The next experimental step was to develop mice with human immune cells capable of the same signaling pathway. When the vaccine live version YFV-17D was applied to them, the cells were susceptible, but gained the usual vaccine immunity in a manner similar to a human immune system. This allowed the researchers to directly study the effect the attenuated virus has on the immune system.

Their modified RNA flow technique allowed them to follow and specifically see the actions of the yellow fever virus within the immune cells. They found that the virus goes after particular immune cells, specifically B lymphocytes and natural killer cells, along with a few others. The virus itself hadn’t been previously found in these particular cells.

Another discovery was that the target immune cells changed over the lifespan of the virus, meaning that the virus may be found in different types of immune cells depending on what stage of its life process it is currently at in infecting its host.

The next step the scientists want to conduct is confirming that the virus and attenuated vaccine virus are found in these immune cell types in human patients as well and it isn’t just a mouse specific result. The new viral RNA flow technique now makes them capable of conducting such a test.

Targeting A Life Cycle

Determining which cells become infected may also showcase why some people that get the vaccine develop a case of the full-blown virus, as it may be that they have certain immune cells types that are more susceptible to the attenuated virus.

In addition, understanding the life cycle of the virus and the cells it targets gives scientists many avenues of research to try and cut off its capability to infect a host, allowing many more types of vaccines to be developed. Even against its cousins, dengue and Zika.

The viral RNA flow technique will likely see much use in the coming future as a way to follow the activities of viruses and find ways to target them more directly.

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Study Link

Photo CCs: Yellow Fever Mosquito -a from Wikimedia Commons

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