Thursday , July 7 2022

The protein to kill virus could be the true antiviral hero that he studies



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Researchers have identified a protein that can kill viruses and constitutes the missing track of the body's natural antiviral mechanism that can guide viruses based on their genetic patterns. This recently identified protein is called KHNYN.

The results of the new study of researchers from King's College and University College London have been published in the journal eLife. The study is entitled, "KHNYN is essential because the zinc finger antiviral protein restricts HIV-1 containing grouped CpG dinucleotides. "

The team of researchers explains that the body's antiviral mechanisms are a fundamental study area, as they can help to develop not only vaccines against these viruses, but also medicines to treat them, as well as cancer medications. They discovered that the genetic basis of a virus particle is their RNA. They have previously discovered that a protein called ZAP (protein activated by zinc fingers) can be linked to a special site in the nucleotides of the virus's RNA and the protein is often targeted between a cytosine and a guanosine amino acid (CpG). The inhibition of a ZAP virus depends on the CpG name of your RNA.

Single-row ribonucleic acid, 3d illustration - Credit: nobeastsofierce / Shutterstock

Single-row ribonucleic acid, 3d illustration – Credit: nobeastsofierce / Shutterstock

There have been research to show that the HIV1 virus has less CpG in its genome. This helps the virus escape from ZAP. The team explained that the presence of the number of CpG in HIV1 viruses determined the rapidity and effectiveness of the virus. When the team could successfully insert a few CpGs in the genomic sequence, ZAP could easily end up with HIV1 viruses, the researchers explained. The next question was how to make the ZAP break the virus's RNA alone.
The first author of this study, Mattia Ficarelli, a PhD student at Chad Swanson's Laboratory of Infectious Diseases, at the King's College in London, said: "Since ZAP can not degrade RNA itself, We have believed that you should recruit other proteins into the viral RNA to destroy it. Thus, in the current study, we proposed identifying new human proteins that are essential for ZAP to guide viral RNAs for their destruction. "

As a result of their investigation, the team has proposed a KHNYN protein that interacts with ZAP. The amount of this protein found recently in the cells that had been infected with the HIV1 virus with a smaller number of CpGs increased. As a comparison, they also took cells infected with HIV1 that were genetically modified to contain more CpGs. The results revealed that when HIV1 had less CpGs, its ability to multiply was more and the addition of KHNYN reduced this ability five times. On the other hand, the multiplication capacity of HIV1 with genetic engineering with more CpG was reduced to 400 times by the addition of KHNYN.

To further his experiment, the team examined the collaboration between ZAP and KHNYN. Cell tools without ZAP and infected with HIV1. Adding the KHNYN protein to these cells was not able to kill them effectively even though the HIV1 viruses in the cells were rich in CpG (a factor that made them more susceptible to ZAP inhibition). On the other hand, they took cells infected with HIV and a mouse leukemia virus with many CpGs and removed KHNYN from them. The results showed that ZAP could not kill these viruses.

Thus, both sets of experiments showed that both ZAP and KHNYN worked in tandem to kill virus particles and other virus particles with more CpGs were more susceptible to these virus slaughtering mechanisms.

Professor Stuart Neil, Department of Infectious Diseases, King's College of London, and the corresponding author of the study, said: "We have identified that KHNYN is necessary for ZAP to prevent HIV from multiplying when it is enriched with CpGs ". The KHNYN protein was probably an enzyme that helps cut the RNA virus after ZAP is linked to it.

Chad Swanson, lead author of the Department of Infectious Diseases, King's College London, added: "A possible interesting application of this work is to make new vaccines or treat cancer. Since some cells Carcinogens have low levels of ZAP, it may be possible to develop CpG rich enriched and cancer killers that do not harm healthy cells. But you need to do many more research to learn more about how ZAP and KHNYN recognize and destroy viral RNA before of being able to explore these applications ".

Magazine's reference:

Mattia Ficarelli, Harry Wilson, Rui Pedro Galão, Michela Mazzon, Irati Antzin-Anduetza, Mark Marsh, Stuart JD Neil, Chad M Swanson, & # 39;KHNYN is essential for Zinc antiviral protein (ZAP) to restrict HIV-1 containing grouped CpG dinucleotides& # 39 ;, eLife 2019; 8: e46767 DOI: 10.7554 / eLife.46767, https://elifesciences.org/articles/46767

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