ELife: discovery of new antiviral protein

August 2, 2019 news / BIOON / - according to the new discovery published in the Journal of eLife, a new protein named khnyn has been identified as a missing part of a natural antiviral system It is very important to study the human body's natural defense to virus and how virus evolves to avoid antiviral mechanism for developing new vaccines, drugs and anti-cancer therapies The genetic information that makes up many viral genomes consists of RNA nucleotides Recently, a protein called zap has been found to bind to specific RNA nucleotide sequences: cytosine and guanosine, or CPG Image source: NIAID human immunodeficiency virus (HIV) is not usually suppressed by zap because it has evolved to have only a small amount of CpG in the genome However, zap promotes the destruction of CPGs when they are added back to the virus This helps us understand why HIV reproduction with more CPG is less successful and may explain why many HIV strains have evolved to have less CPG But a mystery remains, because zap can't break down viral RNA alone "Because zap itself can't degrade RNA, we think it has to recruit other proteins into viral RNA to destroy it," said lead author Mattia ficarelli, a PhD student at Chad Swanson laboratory, Department of infectious diseases, King's college, London "Therefore, in the current research, we have begun to identify new human proteins, which are essential for zap to target viral RNA for destruction "After discovering the interaction between khnyn and zap, the team tested what happened when they increased the amount of khnyn produced in the cells The increase of khnyn production in cells reduced the proliferation of typical HIV by about 5 times, and decreased the proliferation of CpG rich HIV by about 400 times To find out if khnyn and zap work together, the team repeated the same experiment in cells without zap and found that khnyn did not inhibit the proliferation of CpG rich HIV Then they looked at the lack of khnyn in genetically engineered cells and found that both CpG rich HIV and CpG rich mouse leukemia virus were no longer inhibited by zap "We have determined that when CPGs are enriched, zap needs khnyn to prevent the spread of HIV," explained Professor Stuart Neil, co-author of the Department of infectious diseases at King's College London He added that khnyn is likely to be an enzyme that blocks zap binding viral RNA "An interesting potential application of this work is to make new vaccines or treat cancer," added Chad Swanson, senior author and lecturer from the same department Due to the low level of zap in some cancer cells, it is possible to produce CpG rich anti-cancer viruses that will not damage healthy cells But before we continue to explore such applications, more research is needed to understand how zap and khnyn recognize and destroy viral RNA Reference: Mattia ficarelli et al, khnyn is essential for the zinc finger antiviral protein (zap) to restrict HIV-1 containing clustered CpG dinucleotides, eLife (2019) Doi: 10.7554/elife.46767