Host shutoff activity of VHS and SOX-like proteins: role in viral survival and immune evasion

Host shutoff refers to the widespread downregulation of host gene expression and has emerged as a key process that facilitates the reallocation of cellular resources for viral replication and evasion of host antiviral immune responses. The Herpesviridae family uses a number of proteins that are responsible for host shutoff by directly targeting messenger RNA (mRNA), including virion host shutoff (VHS) protein and the immediate-early regulatory protein ICP27 of herpes simplex virus types 1 (HSV-1) and the SOX (shutoff and exonuclease) protein and its homologs in Gammaherpesvirinae subfamilies, although these proteins are not homologous. In this review, we highlight evidence that host shutoff is promoted by the VHS, ICP27 and SOX-like proteins and that they also contribute to immune evasion. Further studies regarding the host shutoff proteins will not only contribute to provide new insights into the viral replication, expression and host immune evasion process, but also provide new molecular targets for the development of antiviral drugs and therapies.