A surprising role for the proteasome in the regulation of herpesvirus infection

Abstract

Recurrent herpes simplex virus (HSV) cold sores in response to cold winter winds or hot summer sunshine are a mere annoyance for most of us, but the ability of the virus to establish a life-long latent infection can have serious clinical consequences. During latency, the viral genome resides in neuronal cell nuclei in a transcriptionally quiescent form, except for the production of a specific set of latency-associated transcripts. Reactivation of the viral genome is characterized by lytic infection of epithelial tissues enervated by the latently infected ganglia1. The mechanisms that govern HSV-1 gene expression, latency and reactivation have intrigued virologists for years. However, studies on viruses have a habit of coming up with surprises that can be relevant to a wider spectrum of molecular and cell biologists. Two topical issues of significant general interest are the functions of the discrete nuclear structures known as ND10 or PML nuclear bodies (reviewed in Ref. 2), and regulation via specific proteasome-mediated proteolysis. Recently, it has been shown that HSV-1 associates with ND10 and then induces proteasome-mediated degradation of component proteins. In addition, proteasome activity is thought to be required for efficient viral lytic infection and reactivation from quiescence. These findings demonstrate another example of the relevance of virology to general biology.