The Grapevine

Why Discovery Of New Virus-Killing Protein Is Important In The Medical Community

A new virus-killing protein working in tandem with another protein has been shown to eliminate viruses related to HIV, the virus that causes AIDS.

This killer protein called “KHNYN” is considered the missing piece in a natural antiviral system that kills viruses by targeting a specific pattern in viral genomese. Studying the body's natural defenses against viruses and how viruses evolve to evade them is crucial to developing new vaccines, drugs and anticancer treatments.

The study published Tuesday in eLife shows KHNYN works together with a known protein called ZAP to eliminate HIV-related viruses. eLife is a  peer-reviewed open access scientific journal for the biomedical and life sciences.

ZAP binds itself to a particular sequence of building blocks that comprise the genetic information of viral genomes. The sequence is called CpG (or a cytosine followed by a guanosine). The building blocks are called RNA nucleotides.

In the past, it wasn’t clear why ZAP couldn’t break down HIV’s viral RNA all by itself. This is where KHNYN came in.

“We believed that ZAP must recruit other proteins to the viral RNA for destroying it, since it cannot degrade RNA by itself,” said Mattia Ficarelli, lead author of the study and a PhD student. “Therefore, in this study, we set out for identifying new human proteins necessary for ZAP for targeting viral RNAs for destruction.”

ZAP and KHNYN were found to reduce a CpG-enriched HIV’s ability to multiply by nearly 400-fold, a remarkable discovery.

“We’ve determined that in order to prevent HIV from multiplying when it’s enriched for CpGs, ZAP requires KHNYN,” said Prof. Stuart Neil, a co-corresponding author of the study from King’s College London’s Department of Infectious Diseases.

The study authors found that KHNYN interacts with ZAP. The viral RNA ZAP binds itself and is probably cut up by KHNYN.

When the scientists raised the amount of KHNYN produced in cells infected with CpG-enriched HIV but without ZAP, KHNYN could not restrict HIV’s ability to multiply. Scientists then examined cells lacking KHNYN. It was found ZAP couldn’t inhibit a mouse leukemia virus having several CpGs and a CpG-enriched HIV on its own.

On the other hand, a CpG-enriched HIV’s ability to multiply was reduced by nearly 400-fold. Also, the ability of a typical HIV with less CpGs was decreased by around five-fold when the amount of KHNYN produced in cells infected with these HIVs was increased.

This showed ZAP and KHNYN work in tandem.

"An interesting potential application of this work is to make new vaccines or treat cancer," said senior author and lecturer Chad Swanson from the Department of Infectious Diseases, King's College London.

"Since some cancer cells have low levels of ZAP, it may be possible to develop CpG-enriched, cancer-killing viruses that would not harm healthy cells. But much more research is necessary to learn more about how ZAP and KHNYN recognise and destroy viral RNA before we can move on to explore such applications."

HIV in Women The initial signs of HIV infection usually involve flu-like symptoms and night sweats. Caroline Hernandez/Unsplash

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