Breakthrough protein discovery could help ‘ZAP’ HIV-related viruses

10 Jul 2019

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A newly identified protein might be the missing piece for an antiviral weapon to destroy viruses related to HIV.

Human immunodeficiency virus (HIV) remains one of humanity’s biggest threats with almost 37m people across the world living with it. While recent developments have greatly improved a person’s chances of living a full life with the virus, a new discovery could significantly boost their quality of life even further.

In a paper published to eLife, researchers from King’s College London announced they had identified a new protein called KHNYN that could be the missing piece of a new antiviral weapon in conjunction with another recently discovered protein.

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

HIV usually evades being ‘zapped’ by ZAP because it has evolved to have few CpGs in its genome. By adding CpGs back into the virus, ZAP becomes a tool of destruction, but why ZAP can’t break down viral RNA by itself has remained a mystery.

This led the researchers to hypothesise that ZAP must recruit other proteins to destroy the viral RNA, eventually leading to the important role played by KHNYN. In lab tests, the newly identified protein was shown to reduce a typical HIV’s ability to multiply about five-fold and decrease the ability of CpG-enriched HIV to multiply by about 400-fold.

The researchers then repeated the experiments in cells without ZAP and found KHNYN couldn’t limit the CpG-enriched HIV from multiplying.

“An interesting potential application of this work is to make new vaccines or treat cancer,” said senior author of the study Chad Swanson.

“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.”

Colm Gorey was a senior journalist with Silicon Republic

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