Does the Zinc Finger Antiviral Protein (ZAP) shape the evolution of Herpesvirus genomes?

Abstract: An evolutionary arms race occurs between viruses and hosts. Hosts have developed an array of antiviral mechanisms aimed at inhibiting replication and spread of viruses, reducing their fitness, and ultimately minimising pathogenic effect. In turn, viruses have evolved sophis-ticated counter-measures that mediate evasion of host defence mechanisms. A key aspect of host defences is the ability to differentiate between self and non-self. Previous studies have demon-strated significant suppression of CpG and UpA dinucleotide frequencies in the coding regions of RNA and small DNA viruses. Artificially increasing these dinucleotide frequencies results in substantial attenuation of virus replication, suggesting dinucleotide bias could facilitate recog-nition of non-self RNA. The interferon inducible gene, zinc finger antiviral protein (ZAP) is the host factor responsible for sensing CpG dinucleotides in viral RNA and restricting RNA viruses through direct binding and degradation of the target RNA.