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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.[1]


History and background

ICP0 was identified as an immediate-early polypeptide product of HSV-1 infection in 1976.[2] 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.[3] This sequence predicted a 775 amino acid sequence with a molecular weight of 78457 Da.[3][4]

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.[5] The RNA transcript accumulates in host cells during latent infection and is known as Latency Associated Transcript (LAT).[5] 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.[6]

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.[7][8] 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).[7]

HSV-1 ICP0 and several of its homologs have been found to bind to SUMO-1 in a manner similar to endogenous proteins.[9] 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.[10][11] ICP0 expression has been shown to result in the depletion of cellular SUMO-1 and the disruption of PML nuclear bodies,[12] while ICP0-homologs in other Herpes viruses have also been shown to disrupt PML nuclear bodies.[13][14][15][10]

Protein cofactor interaction with neuron-differentiating protein NRSF

ICP0 may regulate the expression of some human genes and Herpes virus genes in infected cells.[16][17] ICP0 may interact with a human protein, Neuronal Restrictive Silencer Factor (NRSF)[18], which normally functions to regulate DNA differences between cells.[19] Expression of NRSF determines whether each human cell is a neuron or non-neuronal cell.[20][21] The HSV-1 genome contains an NRSF-binding domain near the beginning of the ICP4 and ICP22 immediate-early genes, which regulates their expression.[17]

ICP0 is partially similar to the human protein CoREST[16], and CoREST normally combines with Neuronal Restrictive Silencer Factor (NRSF, formerly REST[22]) to repress expression of neuronal genes in nonneuronal cells.[19][21] In non-neuronal cells, ICP0 may prevent the silencing of the HSV genome.[18]

In neurons, truncated forms of NRSF may be produced in order to selectively express certain neurotransmitter channels in specialized neurons.[20] 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.[17] The repressed production of these immediate-early HSV genes may contribute to the establishment of latent HSV infection.[17]

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.[17] ICP0 interferes with the HDAC/CoREST/NRSF complex by dissociating HDAC1 from CoREST/NRSF. [16][18] An NRSF-binding DNA has been found between the viral genes expressing proteins ICP4 and ICP22.[17]

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.[23][24] 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).[25] 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[26][27] for HSV-1 ICP0 gene.

Herpes virus ICP-0 homologs and nomenclature
Herpes virus ICP0 Synonyms Homology
HHV-1 Herpes simplex virus-1 (HSV-1) ICP0, IE110 (n/a)
HHV-2 Herpes simplex virus-2 (HSV-2) 61.5% nucleotide sequence homology.[24]
HHV-3 Varicella zoster virus (VZV) ORF-61 Two cell lines expressing VZV ORF-61 are specifically able to support infection by synthetic HSV with ICP0-deletion.[26]
SVV Simian Varicella Virus ORF-61 mRNA is antisense to SVV LAT, as analogous to HSV-1 arrangement of ICP0 and LAT.[25]
PRV Psuedorabies virus EP0 Both HSV-1 ICP0 and VZV ORF-61 complement infection with EP0-deleted synthetic PRV.[28]
HHV-4 Epstein-Barr virus (EBV), lymphocryptovirus BZLF1 Analogous to ICP0 and VZV ORF-61, BZLF1 is SUMO-1 modified and disrupts PML Nuclear Bodies.[9]
HHV-5 Cytomegalovirus (CMV) IE1, IE72[10] Disrupts PML bodies in a manner similar to ICP0.[14]


  • ICP0 blocks the Interferon pathway of cellular host antiviral response which otherwise would lead to production of RNase L and lead to host cell apoptosis. [29]
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.
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