trans-dominant inhibition of herpes simplex virus transcriptional regulatory protein ICP4 by heterodimer formation

Shepard, Alyssa; Tolentino, Paul J.; DeLuca, Neal A.

doi:10.1128/jvi.64.8.3916-3926.1990

Cited by 48 publications

(39 citation statements)

References 44 publications

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“…4,5,6C,7C). The apparent high affinity of the monomer units for each other suggests that dimerization of the 140k DNA binding domain is likely to occur very rapidly after translation, perhaps even concurrently with the polypeptide folding process, as previously proposed for intact ICP4 (52).…”

Section: Discussionsupporting

confidence: 52%

The DNA binding domains of the varicella-zoster virus gene 62 and herpes simplex virus type 1 ICP4 transactivator proteins heterodimerize and bind to DNA

Tyler¹,

Everett²

1994

Nucl Acids Res

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The product of varicella-zoster virus gene 62 (VZV 140k) is the functional counterpart of the major transcriptional regulatory protein of herpes simplex virus type 1 (HSV-1), ICP4. We have found that the purified bacterially expressed DNA binding domain of VZV 140k (residues 417-647) is a stable dimer in solution. As demonstrated by the appearance of a novel protein--DNA complex of intermediate mobility in gel retardation assays, following in vitro co-translation of a pair of differently sized VZV 140k DNA binding domain peptides, the 140k DNA binding domain peptide binds to DNA as a dimer. In addition, the DNA binding domain peptide of HSV-1 ICP4 readily heterodimerizes with the VZV 140k peptide on co-translation, indicating that HSV-1 ICP4 and VZV 140k possess very similar dimerization interfaces. It appears that only one fully wild type subunit of the dimer is sufficient to mediate sequence specific DNA recognition in certain circumstances. Co-immunoprecipitation analysis of mutant DNA binding domain peptides, co-translated with an epitope-tagged ICP4 DNA binding domain, shows that the sequence requirements for dimerization are lower than those necessary for DNA binding.

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Section: Discussionsupporting

confidence: 52%

The DNA binding domains of the varicella-zoster virus gene 62 and herpes simplex virus type 1 ICP4 transactivator proteins heterodimerize and bind to DNA

Tyler¹,

Everett²

1994

Nucl Acids Res

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“…ICP4 antibodies include the 889 mouse monoclonal antibody 58S ( Figure 1A and S4) (Showalter et al, 1981) and the rabbit 890 polyclonal antibody N15 ( Figure S2). 58S only recognizes the dimeric form of ICP4, which 891 binds to viral DNA (Shepard et al, 1990). Images were obtained using an Olympus Fluoview 892 FV1000 confocal microscope.…”

Section: Viral Genome Imaging and Immunofluorescence 877mentioning

confidence: 99%

Temporal Viral Genome-Protein Interactions Define Distinct Stages of Productive Herpesviral Infection

Dembowski

DeLuca

2018

Preprint

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29Herpesviruses utilize multiple mechanisms to redirect host proteins for use in viral 30 processes and to avoid recognition and repression by the host. To investigate the dynamic 31 interactions between HSV-1 DNA and viral and host proteins, we developed an approach to 32 identify proteins that associate with the infecting viral genome from nuclear entry through 33 packaging. We found that input viral DNA progressed within six hours through four temporal 34 stages where the genomes: 1. interacted with intrinsic and DNA damage response proteins, 35 2. underwent a robust transcriptional switch mediated largely by ICP4, 3. engaged in 36 replication, repair, and continued transcription, and then 4. transitioned to a more 37 transcriptionally inert state engaging de novo synthesized viral structural components while 38 maintaining interactions with replication proteins. Using a combination of genetic, imaging, 39 and proteomic approaches, we provide a new and temporally compressed view of the HSV-1 40 life cycle based on genome-proteome dynamics. 41 42 43

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“…Gel retardation assays. The wt and mutant ICP4 proteins used for the assays were purified from infected cells harvested at 12 to 15 h postinfection as previously described (27,65,67). Bacterial expression and purification of recombinant human TBP and TFIIB were performed as described by Kao et al (28) and Ha et al (21), respectively, with minor modifications (69).…”

Section: Virus and Cells Vero Cells And The Complementing Cell Linesmentioning

confidence: 99%

Functional interactions between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4

Samaniego

Webb

DeLuca

1995

J Virol

Self Cite

118

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Two of the five immediate-early gene products, ICP4 and ICP27, expressed by herpes simplex virus type 1 have profound effects on viral gene expression and are absolutely essential for virus replication. Functional interactions between ICP4 and ICP27 may contribute to establishing the program of viral gene expression that ensues during lytic infection. To evaluate this possibility, viral mutants simultaneously deleted for ICP27 and defined functional domains of ICP4 were constructed. These mutant viruses allowed a comparison of gene expression as a function of different domains of ICP4 in the presence and absence of ICP27. Gene expression in the absence of both ICP4 and ICP27 was also examined. The results of this study demonstrate a clear involvement for ICP27 in the induction of early genes, in addition to its known role in enhancing late gene expression during viral infection. In the absence of both ICP4 and ICP27, viral early gene expression, as measured by the accumulation of thymidine kinase and ICP6 messages was dramatically reduced relative to the amounts of these messages seen in the absence of only ICP4. Therefore, elevated levels of early gene expression as a consequence of ICP27 occurred in the absence of any ICP4 activity. Evidence is also presented regarding the modulation of the ICP4 repression function by ICP27. When synthesized in the absence of ICP27, a mutant ICP4 protein was impaired in its ability to repress transcription from the L/ST promoter in the context of viral infection and in vitro. This defect correlated with the loss of the ability of this mutant protein to bind to its recognition sequence when produced in infected cells in the absence of ICP27. These observations indicate that ICP27 can regulate the activity of at least one domain of the ICP4 protein as well as contribute to elevated early gene expression independently of ICP4.

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trans-dominant inhibition of herpes simplex virus transcriptional regulatory protein ICP4 by heterodimer formation

Cited by 48 publications

References 44 publications

The DNA binding domains of the varicella-zoster virus gene 62 and herpes simplex virus type 1 ICP4 transactivator proteins heterodimerize and bind to DNA

The DNA binding domains of the varicella-zoster virus gene 62 and herpes simplex virus type 1 ICP4 transactivator proteins heterodimerize and bind to DNA

Temporal Viral Genome-Protein Interactions Define Distinct Stages of Productive Herpesviral Infection

Functional interactions between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4

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