Role of ICP0 in the Strategy of Conquest of the Host Cell by Herpes Simplex Virus 1

Abstract

In early studies, herpes simplex virus 1 (HSV-1) proteins were identified on the basis of two criteria. The first consisted of characterization of proteins contained in virions purified from cells whose proteins were labeled prior to infection. These proteins designated by the prefix VP were numbered in the order of decreasing apparent molecular weight or, conversely, ascending electrophoretic mobility in denaturing gels (147). The second criterion identified putative viral proteins accumulating in infected cells but absent from uninfected cells. These proteins, designated infected-cell proteins (ICPs), were also numbered in order of decreasing apparent molecular weight (73). One protein, however, while clearly apparent only in infected cells, varied with respect to electrophoretic mobility depending on the composition of the denaturing gel (74). This anomalously migrating protein was designated ICP0 (74). In subsequent studies, viral proteins were designated either by their known primary function (e.g., DNA polymerase, etc.) or the position of the gene along the unique long (U L ) or short (U S ) components of the viral genome (105, 107). The original ICP designation, however, was retained primarily for five proteins recognized in early studies as being the products of ␣ or immediate-early genes expressed after infection in the absence of de novo viral protein synthesis (74, 75). The five proteins, ICP0, ICP4, ICP22, ICP27, and ICP47, have been extensively studied, and for the most part, there is at least a semblance of concordance between the phenotype of cells infected with the mutant lacking the gene, the behavior of the protein in transduced cells, and the molecular functions expressed by the protein (reviewed in reference 132). ICP4 is an essential positive and negative regulator of gene expression (reviewed in reference 132). The protein blocks gene expression by binding to high-affinity DNA consensus sites located at transcription initiation sites of at least two genes. The mechanism of gene activation is less understood, although ICP4's affinity for transcription factors and binding to highly degenerate or nonconsensus sites are suggestive of how it might act. ICP27 is also a multifunctional protein whose phenotype can be largely explained by its ability to block RNA splicing but not transport of unspliced RNA early in infection and by its activity as a chaperone of newly made viral mRNA across the nuclear membranes at late times after infection (reviewed in reference 137).Available data indicate that the carboxyl-terminal half of ICP22 enables full expression of a subset of late (␥ 2 ) viral genes by causing cdc2 cyclin-dependent kinase activity to survive the degradation of its physiologic partners cyclins A and B, by an aberrant partnership with the U L 42 DNA polymerase processivity factor (2,5,6,19,141). Optimal transcription of late genes requires binding and posttranslational modification of topoisomerase II␣ by the two proteins (7). The sole known mission of ICP47 is to bind to and preclude TAP1...

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

“…Another immediate-early protein, ICP0, influences the host cell by inducing the degradation of specific cellular proteins and disturbing cellular structures (Hagglund & Roizman, 2004;Parkinson & Everett, 2000). Other viral genes such as U L 41 and c 1 34.5 influence the surface expression of MHC class II molecules (Trgovcich et al, 2002).…”

Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells

“…As noted in detail in ref. 10, these studies indicate that ICP0 does not enable viral gene expression by mediating the degradation of ND10 structures. A significant clue to the role of ICP0 is the observation that it transactivates the expression of viral or cellular genes introduced by infection or transfection, even though it does not bind DNA directly and is not known to bind known transcriptional factors.…”

“…As reviewed in ref. 10, ICP0 is extensively posttranslationally modified by viral (U L 13) and cellular (cdc2) protein kinases and is nucleotidylated by casein kinase II. The protein physically interacts with the translation-elongation factor 1␦, cyclin D3, the ubiquitinconjugating enzyme UbcH3 (cdc34), the ubiquitin-specific protease 7, the transcriptional factor BML1, and a protein designated as p60.…”

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

“…It remains unclear whether HCV core induces proteosome-mediated core11 degradation. However, there is growing evidence that proteosome activity may be directed by a diverse range of viral proteins as part of an efficient viral propagation strategy (61)(62)(63)(64)(65)(66)(67). Indeed, it was recently reported that the core protein of HBV stimulates the proteasome-mediated degradation of the HBV X protein (HBX), when the HBV viral proteins, which are transcriptionally transactivated by the X protein, reach a sufficiently high levels for viral replication (68)(69)(70)(71)(72).…”