Newly Identified Protein (KHNYN) Works with ZAP Protein to Promote Destruction of HIV Virus Containing Clustered CpG Dinucleotides

A newly identified protein called KHNYN teams up with ZAP (image), a known virus-killing protein, to destroy viruses related to HIV. KHNYN has been identified as a missing piece in a natural antiviral system that kills viruses by targeting a specific pattern in viral genomes, according to new findings published online on July 9, 2019 in eLife. The open-access article is titled “KHNYN Is Essential for the Zinc Finger Antiviral Protein (ZAP) to Restrict HIV-1 Containing Clustered CpG Dinucleotides.” Studying the body's natural defenses to viruses and how viruses evolve to evade them is crucial to developing new vaccines, drugs, and anticancer treatments. The genetic information that makes up the genomes for many viruses is comprised of building blocks called RNA nucleotides. Recently, it was discovered that a protein called ZAP binds to a specific sequence of RNA nucleotides: a cytosine followed by a guanosine, or CpG for short. The human immunodeficiency virus (HIV) normally escapes being inhibited by ZAP because it has evolved to have few CpGs in its genome. However, when CpGs are added back to the virus, ZAP promotes its destruction. This helps us understand why HIV with more CpGs multiplies less successfully, and likely explains why many strains of HIV have evolved to have few CpGs. But a mystery remained because ZAP is unable to break down the viral RNA by itself. "As ZAP can't degrade RNA on its own, we believed that it must recruit other proteins to the viral RNA to destroy it," says lead author Mattia Ficarelli, a PhD student in Dr. Chad Swanson's Lab, Department of Infectious Diseases, King's College London.