Our innate immune system cells contain intrinsic antiviral proteins, such as the ZAP protein, that can identify and target viral RNAs by binding to a combination of no more than two nucleotides called CpG. HIV, along with many other viruses, found a way to bypass this defense mechanism. Nevertheless, it has been found that the ZAP protein doesn’t cut RNA on its own. Other unidentified molecules seems to take part in this process since they have fewer CpG.
Ficarelli & al identified a protein with no previously known function, KHNYN, that interacts with ZAP. They first genetically modified the RNA of the HIV virus in order to make it CpG enriched. They then showed that an increased amount of KHNYN protein lowers levels of HIV RNAs with high CpG.
They found that in mutant cells lacking KHNYN, CpG enriched viruses were able to multiply in a better way than in the normal cells. To make sure that a certain region KHNYN is the one that cut RNA, the team mutated that region and this resulted in its inability to inhibit the multiplication of CpG enriched HIV.
The exact interaction between the ZAP and KHNYN proteins needs to be characterized. This discovery of a natural ZAP partner in virus killing opens the door for plenty of future applications in human health. For instance, vaccines could use CpG enriched weakened viruses. As the authors suggested, it could be very useful in tumors with decreasing levels of ZAP, by engineering viruses degradable by healthy cells but could multiply in and kill cancer cells.
Full research article here
An inefficient virus kills its host. A clever virus stays with it.
– James Lovelock –
Biological culture 
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