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HHV Infected Cell Polypeptide 0 (ICP0)
Human Herpes Virus (HHV) Infected Cell Polypeptide 0 (ICP0) is a protein produced by Herpes viruses during the earliest stage of infection, when the herpes virus has recently entered the host cell. This stage is known as the immediate-early or α ("alpha") phase of Herpes virus gene expression.
Additional recommended knowledge
History and background
ICP0 was identified as an immediate-early polypeptide product of HSV-1 infection in 1976. The gene from which ICP0 is produced is known as HSV-1 α0 ("alpha zero") and formerly as Immediate Early (IE) gene 1. However, the gene is also referred to as the HSV-1 ICP0 gene. The HSV-1 ICP0 gene was characterized and sequenced in 1986. This sequence predicted a 775 amino acid sequence with a molecular weight of 78457 Da.
Antisense interaction with latency-associated RNA transcript (LAT)
During latent infection a viral RNA transcript inhibits expression of the Herpes virus ICP0 gene via an antisense RNA mechanism. The RNA transcript accumulates in host cells during latent infection and is known as Latency Associated Transcript (LAT). Study of the HSV-1 genome has located a chromatin insulator region between LAT and ICP0 gene promoters which may allow for the independent regulation of their expression.
ICP0 and homologs interact with host cell SUMO-1 protein and disrupt PML Nuclear Bodies
SUMO-1 is a ubiquitin-related protein produced by human cells. A normal function of SUMO-1 appears to be modification of the human PML protein so that PML localizes in the nucleus where it becomes a part of the PML nuclear bodies (or ND10 structures).
HSV-1 ICP0 and several of its homologs have been found to bind to SUMO-1 in a manner similar to endogenous proteins. HSV-1 ICP0-family proteins have also been shown to disrupt the formation of nuclear bodies in a manner which depends on this activity of ICP0. ICP0 expression has been shown to result in the depletion of cellular SUMO-1 and the disruption of PML nuclear bodies, while ICP0-homologs in other Herpes viruses have also been shown to disrupt PML nuclear bodies.
Protein cofactor interaction with neuron-differentiating protein NRSF
ICP0 may regulate the expression of some human genes and Herpes virus genes in infected cells. ICP0 may interact with a human protein, Neuronal Restrictive Silencer Factor (NRSF), which normally functions to regulate DNA differences between cells. Expression of NRSF determines whether each human cell is a neuron or non-neuronal cell. The HSV-1 genome contains an NRSF-binding domain near the beginning of the ICP4 and ICP22 immediate-early genes, which regulates their expression.
ICP0 is partially similar to the human protein CoREST, and CoREST normally combines with Neuronal Restrictive Silencer Factor (NRSF, formerly REST) to repress expression of neuronal genes in nonneuronal cells. In non-neuronal cells, ICP0 may prevent the silencing of the HSV genome.
In neurons, truncated forms of NRSF may be produced in order to selectively express certain neurotransmitter channels in specialized neurons. In neurons, ICP0 may combine with NRSF-like neuronal factors to silence immediate-early genes, possibly blocking the production of ICP4 and possibly reducing production of ICP22. The repressed production of these immediate-early HSV genes may contribute to the establishment of latent HSV infection.
CoREST and NRSF normally combine with another cellular protein, histone deacetylase-1 (HDAC). A study confirms that this complex silences production of HSV-1 protein ICP4 via deacetylation of the histones around which viral DNA chromatin is packed. ICP0 interferes with the HDAC/CoREST/NRSF complex by dissociating HDAC1 from CoREST/NRSF.  An NRSF-binding DNA has been found between the viral genes expressing proteins ICP4 and ICP22.
Homologs across Herpes virus species
The HSV-1 ICP0 gene and protein have corresponding homologs in related viruses from the Herpes virus family. The reported sequence for HSV-2 ICP0 is predicted to produce a polypeptide comprised of 825 amino acids with a predicted molecular weight of 81986 Da, and 61.5% amino acid sequence similarity to HSV-1 ICP0. Simian Varicella Virus (SVV) is a Varicellovirus (a Genus of Subfamily Alphaherpesvirinae) which expresses an HHV LAT homolog known as SVV LAT, and an HHV ICP0 analog known as SVV ORF-61 (Open Reading Frame 61). Varicella Zoster Virus (VZV) is another Varicellovirus in which a homolog of HSV-1 ICP0 gene has been identified; VSV ORF-61 is a partial homolog and a functional replacement for HSV-1 ICP0 gene.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "HHV_Infected_Cell_Polypeptide_0_(ICP0)". A list of authors is available in Wikipedia.|