Self-Interaction of the Herpes Simplex Virus Type 1 Regulatory Protein ICP27

Zhi, Yan; Sciabica, Kathryn S.; Sandri‐Goldin, Rozanne M.

doi:10.1006/viro.1999.9698

Cited by 58 publications

(100 citation statements)

References 48 publications

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“…1, line 6), were repeated three times with the same negative result, while control rOka virus was consistently generated. This result supported the evidence that the ICP27 of HSV-1 functions as a multimer (14).…”

supporting

confidence: 87%

Requirement of Varicella-Zoster Virus Immediate-Early 4 Protein for Viral Replication

Sato

Sommer

Ito

et al. 2003

J Virol

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Varicella-zoster virus (VZV) is an alphaherpesvirus that causes two diseases, chickenpox and zoster. VZVopen reading frame 4 (ORF4) encodes the immediate-early 4 (IE4) protein, which is conserved among alphaherpesvirus and has transactivation activity in transient transfections. To determine whether the ORF4 gene product is essential for viral replication, we used VZV cosmids to remove ORF4 from the VZV genome. Deleting ORF4 was incompatible with recovery of infectious virus, whereas transfections done by using repaired cosmids with ORF4 inserted at a nonnative site yielded virus. To analyze the functional domain of IE4, we introduced a mutation altering the C-terminal amino acids, KYFKC (K443S), which was designed to disrupt the dimerization of IE4 protein. Transfections with these mutant cosmids yielded no virus, indicating that this KYFKC motif was essential for IE4 function.Varicella zoster virus (VZV) is a ubiquitous human alphaherpesvirus which causes varicella (chickenpox) during primary infection and herpes zoster (shingles) after its reactivation from sites of latency in sensory ganglia (1, 3). Both varicella and zoster continue to be serious public health problems (1, 11). The expression of VZV genes is regulated in a temporal fashion known as the lytic cascade. The product of open reading frame 4 (ORF4) has been shown to have immediate-early regulatory functions, like immediate-early 62 (IE62) and IE63 (4). The IE4 tegument protein is a 51-kDa phosphoprotein that transactivates genes of all three kinetic classes in transient expression systems and enhances IE62 transactivation (4). In turn, IE62, along with the cellular transcription factor USF, activates the ORF4 promoter (7). IE4 protein resembles its herpes simplex virus (HSV) homolog, ICP27, in its C-terminal residues (38% in amino acids 235 to 449) and complements ICP27 functions in this region, but it does not repair full deletions of the ICP27 gene (8, 9). The equine herpesvirus homolog is UL3 (12). Baudoux et al. have recently mapped IE4 domains in transient expression systems (2), demonstrating that the IE4 transactivating function depends on dimerization mediated by a KYFKC peptide in the C-terminal cysteine-rich region, amino acids 443 to 447. Other mutations in an arginine-rich region of the amino terminus, designated Rb, also reduced transactivation independently of dimerization and may be required for IE4 interactions with cellular proteins, including TATA-binding protein, transcription factor IIB, and the p50 and p65 subunits of NF-B (5). IE4 also has KH-like motifs that are involved in RNA binding which are found in conserved forms in alphaherpesvirus homologs and are required for HSV replication (13).The aim of this report was to examine the role of IE4 protein in viral replication by deleting or mutating ORF4 in the context of the viral genome. We showed that ORF4 is an essential gene and that the sequence encoding the C-terminal KYFKC motif in IE4 protein, which mediates dimerization, is required for VZV replication. Effect of ORF4 ...

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supporting

confidence: 87%

Requirement of Varicella-Zoster Virus Immediate-Early 4 Protein for Viral Replication

Sato

Sommer

Ito

et al. 2003

J Virol

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“…It is more likely that alterations in the C terminus of ICP27 cause misfolding of the protein or structural changes, which deleteriously affect its functions. ICP27 requires its C terminus for self-interaction, and it is interesting to speculate that this self-interaction may be required for ICP27 to function properly (50).…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus ICP27 Increases Translation of a Subset of Viral Late mRNAs

Fontaine-Rodriguez

Knipe

2008

J Virol

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The herpes simplex virus (HSV) ICP27 immediate-early protein plays an essential role in the expression of viral late genes. ICP27 is a multifunctional protein and has been reported to regulate multiple steps of mRNA synthesis and processing, including transcription, splicing, and nuclear export. Recently, ICP27 was reported to interact with translation factors and to stimulate translation of the viral late mRNA encoding VP16. We examined the effects of ICP27 on accumulation, nuclear export, and translation of HSV 1 (HSV-1) late mRNAs encoding VP16, ICP5, and gD. We confirm here that ICP27 stimulates translation of VP16 mRNA as well as an additional HSV-1 late ICP5 mRNA. The data presented here demonstrate that translation levels of both VP16 and ICP5 mRNA is reduced during infections with the ICP27-null virus mutant d27-1, and with ICP27 C-terminal deletion mutant viruses n406 and n504, compared to wild-type virus. In contrast, the translation of gD mRNA is not affected by the presence of ICP27 during infection. These data demonstrate that ICP27 functions to increase the translation levels of a subset of HSV-1 late genes, and this function requires the C terminus of ICP27.

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“…Several reports have demonstrated roles for viral kinases (US3 and UL13) and certain cellular kinases (PKA, PKC, CKI, JNK1 or CDC2) in modifications of HSV-1 IE proteins (11)(12)(13)(14)(15). Conversely, HSV-1 enzymes may also alter the regulation of PTMs on host proteins and histones.…”

Section: Herpes Simplex Virus (Hsv-1)mentioning

confidence: 99%

“…and is extensively employed by virus and host (11)(12)(13)(14)(15). We therefore analyzed the phosphoproteome of both viral and cellular proteins over the time course of HSV-1 infection.…”

Section: Phosphoproteomics Analysis Of Host and Viral Proteome Duringmentioning

confidence: 99%

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection

Kulej

Avgousti

Sidoli

et al. 2017

Molecular & Cellular Proteomics

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Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection. We analyzed proteomes across six time points of virus infection (0, 3, 6, 9, 12 and 15 h post-infection) and clustered trends in abundance using fuzzy c-means. Globally, we accurately quantified more than 4000 proteins, 200 differently modified histone peptides and 9000 phosphorylation sites on cellular proteins. In addition, we identified 67 viral proteins and quantified 571 phosphorylation events (465 with high confidence site localization) on viral proteins, which is currently the most comprehensive map of HSV-1 phosphoproteome. We investigated chromatin bound proteins by proteomic analysis of the high-salt chromatin fraction and identified 510 proteins that were significantly different in abundance during infection. We found 53 histone marks significantly regulated during virus infection, including a steady increase of histone H3 acetylation (H3K9ac and H3K14ac). Our data provide a resource of unprecedented depth for human and viral proteome dynamics during infection. Collectively, our results indicate that the proteome composition of the chromatin of HFF cells is highly affected during HSV-1 infection, and that phosphorylation events are abundant on viral proteins. We propose that our epi-proteomics approach will prove to be important in the characterization of other model infectious systems that involve changes to chromatin composition. Molecular & Cellular Proteomics 16: 10.1074/mcp.M116.065987, S92-S107, 2017. Herpes simplex virus (HSV-1)1 leads to a contagious and persistent infection that affects about 95% of the human population. The HSV-1 genome is a double-stranded DNA molecule that replicates in the host cell nucleus (1). HSV-1 initially infects epithelial cells as a lytic infection, and then enters peripheral neurons where it establishes latency (2, 3). Processes such as viral transcription, viral DNA synthesis, virion assembly and DNA packaging take place in discrete virus-induced structures within the nucleus called replication compartments (1, 4). These processes are temporally regulated by the viral cascades of immediate-early (IE), early (E), and late (L) gene expression. The IE proteins are primarily responsible for counteracting intrinsic host defenses and for activating expression of early-phase genes (1). Early viral pro-

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Self-Interaction of the Herpes Simplex Virus Type 1 Regulatory Protein ICP27

Cited by 58 publications

References 48 publications

Requirement of Varicella-Zoster Virus Immediate-Early 4 Protein for Viral Replication

Requirement of Varicella-Zoster Virus Immediate-Early 4 Protein for Viral Replication

Herpes Simplex Virus ICP27 Increases Translation of a Subset of Viral Late mRNAs

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection

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