herpes simplex virus 1 (HHV-1) ICP0 protein; RING sinkkisormen sisältävä E3 ubikitiiniligaasi

 herpes simplex virus 1 (HHV-1) ICP0 protein; 

. Author manuscript; available in PMC: 2012 Feb 1.

Published in final edited form as: Future Virol. 2011 Apr;6(4):421–429. doi: 10.2217/fvl.11.24

HSV-1 ICP0: paving the way for viral replication

Miles C Smith 1, Chris Boutell 2, David J Davido 1,†

PMCID: PMC3133933  NIHMSID: NIHMS303334  PMID: 21765858

The publisher's version of this article is available at Future Virol

Abstract

Herpes simplex virus type 1 (HSV-1) has two distinct phases of its viral life cycle: lytic and latent. One viral immediate-early protein that is responsible for determining the balance between productive lytic replication and reactivation from latency is infected cell protein 0 (ICP0). ICP0 is a 775-amino acid really interesting new gene (RING)-finger-containing protein that possesses E3 ubiquitin ligase activity, which is required for ICP0 to activate HSV-1 gene expression, disrupt nuclear domain (ND) 10 structures, mediate the degradation of cellular proteins, and evade the host cell’s intrinsic and innate antiviral defenses. This article examines our current understanding of ICP0’s transactivating, E3 ubiquitin ligase, and antihost defense activities and their inter-relationships to one another. Lastly, we will discuss how these properties of ICP0 may be utilized as possible targets for HSV-1 antiviral therapies.

Keywords: E3 ubiquitin ligase, herpes simplex virus, ICP0, innate immunity, intrinsic defense, nuclear domain 10, viral transactivator

The requirement for ICP0 during viral replication

The importance of infected cell protein 0’s (ICP0’s) role in productive infection and reactivation from latent infections was initially identified from characterizing the replication phenotypes of ICP0-null mutants in cell culture. These early reports showed that ICP0 confers a significant growth advantage during replication, especially at low multiplicities of infection [1–5]. Consistent with cell culture experiments, ICP0-null mutants were subsequently shown to be attenuated for viral growth [5–8] and impaired for viral reactivation when equivalent latent infections were established in vivo [9]. Collectively, these studies indicated that ICP0 is required for efficient replication and reactivation from latency.