The protein killing the virus could be the real antiviral discovers a study

Researchers have identified a protein that can kill viruses. It is a missing clue to the body's natural antiviral mechanism that can target viruses based on their genetic structure. This newly identified protein is called KHNYN.

The results of the new study by researchers at King's College and University College London have been published in the journal eLife. The study is entitled "KHNYN is essential for zinc finger antiviral protein to limit CpG dinucleotides into clusters containing HIV-1. "

The research team says the body's antiviral mechanisms are a critical area of ​​study because they can help develop not only vaccines against these viruses, but also drugs to treat them, as well as anti-cancer drugs. They discovered that the genetic basis of a viral particle is its RNA. They had previously discovered that a protein called ZAP (Zinc Finger Protein) could bind to a particular place in the nucleotide RNAs of the virus and that the protein was often sandwiched between a cytosine and a guanosine amino acid. (CpG). The inhibition of a virus by ZAP depends on the number of CpG on its RNA.

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

Research has shown that the HIV1 genome has less CpG. This helps the virus to escape the ZAP. The team explained that the presence of CpG on HIV1 determined the speed and efficiency of virus multiplication. When the team was able to insert some CpGs into its genomic sequence, ZAP could easily eliminate the HIV1 virus, the researchers explained. The next question was how to ensure that ZAP breaks down the RNA of the virus by itself.
The first author of this study, Mattia Ficarelli, Ph.D. student at Chad's Swanson College's Infectious Diseases Department of King's College London, said: "Since ZAP can not degrade the RNA by itself, viral RNA to destroy it. Thus, in this study, we sought to identify new human proteins that are essential for ZAP to target viral RNAs for destruction. "

As a result of their investigation, the team has developed a KHNYN protein that interacts with ZAP. They increased the amount of this newly found protein in HIV1-infected cells with a smaller number of CpGs. As a comparison, they also took HIV1-infected cells genetically engineered to contain more CpG. The results revealed that when HIV1 had less CpG, its ability to multiply was greater and the addition of KHNYN reduced it five times. Moreover, the multiplication capacity of genetically modified HIV1 with more CpG was reduced up to 400 times by the addition of KHNYN.

To deepen their experience, the team then examined the collaboration between ZAP and KHNYN. They equip the cells without ZAP and infect them with HIV1. The addition of KHNYN protein to these cells failed to kill them effectively despite the fact that the HIV1 viruses in the cells were rich in CpG (a factor that made them more likely to be present in the cells). inhibition of ZAP). On the other hand, they took HIV-infected cells and a mouse leukemia virus containing many CpGs and removed them from KHNYN. The results showed that the ZAP was unable to kill these viruses.

Thus, both sets of experiments proved that ZAP and KHNYN were working in tandem to kill viral particles and that other viral particles with more CpG were more susceptible to these viral killing mechanisms.

Professor Stuart Neil, from the Department of Infectious Diseases at King's College London, and corresponding author of the study, said, "We have identified the need for KHNYN for the ZAP to prevent HIV from occurring. multiply when it is enriched for CpG. "The KHNYN protein was probably an enzyme that helps cut the virus's RNA after ZAP binding.

Keynote speaker, Chad Swanson, from the Department of Infectious Diseases at King's College London, added, "An interesting potential application of this work is the manufacture of new vaccines or the treatment of cancer. 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. "