36] Herpes simplex virus vhs protein

Abstract

Publisher Summary The virion host shutoff (vhs) protein encoded by herpes simplex virus (HSV) gene UL41 is responsible for the rapid shutoff of host protein synthesis that occurs during the earliest stages of HSV infection. This chapter summarizes the current understanding of the mechanism of action and regulation of vhs activity, and provides a detailed description of a simple and convenient In Vitro assay for vhs-dependent ribonuclease activity. vhs is a structural component of the HSV virion that is synthesized late in infection and packaged into the tegument of the mature virus particle (the space between the envelope and the nucleocapsid). It is then delivered into the cytoplasm of newly infected cells after fusion of the virion envelope with the host plasma membrane, where it triggers host shutoff before the onset of de novo viral gene expression, vhs-induced shutoff is characterized by strong inhibition of host protein synthesis, disruption of preexisting polyribosomes, and accelerated turnover of host mRNAs. The vhs-dependent shutoff system exhibits little specificity, destabilizing most, if not all, cellular and viral mRNAs in the infected cell. The rapid decline in host mRNA levels presumably helps viral mRNAs gain access to the cellular translational apparatus. The vhs system provides a striking and readily dissected example of gene regulation at the level of mRNA stability in mammalian cells, and may therefore help illuminate the host mRNA turnover pathways that regulate cell growth, differentiation, and oncogenesis.