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Revolutionary protein discovery could help HIV-related "ZAP" viruses

A newly identified protein could be the missing element of an antiviral weapon to destroy HIV-related viruses.

The human immunodeficiency virus (HIV) remains one of the greatest threats to humanity, with nearly 37 million people worldwide. While recent developments have greatly improved a person's chances of living fully with the virus, a new discovery could dramatically improve their quality of life.

In an article published in eLife, researchers at King's College London have announced that they have identified a new protein called KHNYN, which could be the missing element of a new antiviral weapon associated with another recently discovered protein.

The genetic information that makes up the genomes of many viruses include building blocks called nucleotides of RNA. The previously discovered protein, ZAP, binds to a specific sequence of RNA nucleotides: a cytosine followed by a guanosine, or abbreviated CpG.

HIV generally avoids being "zapped" by ZAP because it has evolved to have little CpG in its genome. By adding CpGs into the virus, ZAP becomes a tool of destruction, but the reason ZAP can not break down viral RNA as such has remained a mystery.

The researchers then hypothesized that ZAP would have to recruit other proteins to destroy the viral RNA, which would ultimately lead to the important role played by KHNYN. In laboratory tests, the newly identified protein has been shown to reduce the typical HIV capacity to approximately five-fold increase and decrease the ability of CpG-enriched HIV to multiply by approximately 400.

The researchers then repeated the experiments in ZAP-free cells and found that KHNYN could not prevent the multiplication of CpG-enriched HIV.

"An interesting potential application of this work is to make new vaccines or treat cancer," said lead author Chad Swanson.

"Since some cancer cells have low levels of ZAP, it may be possible to develop CpG-enriched anticancer viruses that would not harm healthy cells. But there is still a lot of research to be done on how ZAP and KHNYN recognize and destroy viral RNA before they can explore such applications. "

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