Physical and functional interactions between herpes simplex virus immediate-early proteins ICP4 and ICP27

Panagiotidis, Christos Α.; Lium, E K; Silverstein, Saul

doi:10.1128/jvi.71.2.1547-1557.1997

Cited by 67 publications

(34 citation statements)

References 100 publications

(177 reference statements)

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“…Infection with ICP27 mutants, however, results in accumulation of ICP0 and ICP4 exclusively in the nucleus (100)(101)(102). Finally, ICP27 is implicated in the posttranslational modifications of ICP0 and ICP4, and it has been suggested that, in the absence of ICP27, ICP4 may not be phosphorylated (65,73).…”

Section: Fig 2 Infection With Uv-irradiated Hsv Does Not Results In mentioning

confidence: 99%

Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38

Hargett¹,

McLean²,

Bachenheimer

2005

J Virol

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We previously reported that herpes simplex virus type 1 (HSV-1) can activate the stress-activated protein kinases (SAPKs) p38 and JNK. In the present study, we undertook a comprehensive and comparative analysis of the requirements for viral protein synthesis in the activation of JNK and p38. Infection with the UL36 mutant tsB7 or with UV-irradiated virus indicated that both JNK The stress-activated protein kinases (SAPKs) p38 and JNK are part of a larger family of serine/threonine terminal kinases termed mitogen-activated protein kinases (MAPK), which includes ERK1 and -2. SAPK pathways are normally activated by UV irradiation, anoxia, and engagement of proinflammatory cytokines or Fas ligand by their cognate receptors. Following ligand binding to a cognate receptor, signaling is initiated through receptor-associated kinases to a MAPKKK (MAPK kinase kinase). MAPKKKs capable of initiating the p38 or JNK pathway include MEKK1, -2, -3, and -4, ASK-1, TAK-1, and TAO. These in turn activate dual-specificity MAPK kinase kinases (MAPKKs) MKK3/6 and MKK4/7, which directly bind and phosphorylate p38 and JNK, respectively, on both tyrosine and threonine, resulting in their activation (for a review, see reference 78).All three subfamilies of human herpesviruses activate one or more of the MAPKs during infection. The betaherpesvirus cytomegalovirus activates both p38 and ERK by a mechanism dependent on viral gene expression (14,39,76) and the upstream kinases MKK3/6 and MKK1/2, respectively, (39, 40). ERK activates the early gene UL112-113 promoter (76) and phosphorylates immediate-early 86 and 72 proteins to alter their transactivation activity (40), while p38 phosphorylates retinoblastoma protein and HSP27 (39). ERK and p38 activation are required for cytomegalovirus DNA replication (16). The gammaherpesvirus Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor activates ERK and p38, causing increased vascular endothelial growth factor expression via phosphorylation of hypoxia-inducible factor 1␣ (86). The gammaherpesvirus Epstein-Barr virus activates p38 and JNK (1, 21). The immediate-early proteins BZLF1 and BRLF1 induce increased phosphorylation of p38 and JNK and activation of the ATF-2 transcription factor (1). BZLF1 expression during BRLF1-driven virus reactivation requires p38 activity (1). Among the alphaherpesviruses, HSV-2 has been reported to activate ERK through ICP10-PK binding to RAS-GAP, leading to further expression of ICP10 and prevention of apoptosis (68).Two previous reports documented the activation of the p38 and JNK (SAPK) pathways by HSV-1. Increased JNK and p38 kinase activity was observed as early as 3 hours postinfection and remained active throughout the course of infection (56,97). SAPKs were activated downstream of Ras, as infection with a dominant-negative form of Ras did not affect activation of the transcription factors ATF-2 and c-Jun, downstream targets of p38 and JNK, respectively (56). Furthermore, activation was specific for SAPKs, as ERK was not activated during infect...

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Section: Fig 2 Infection With Uv-irradiated Hsv Does Not Results In mentioning

confidence: 99%

Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38

Hargett¹,

McLean²,

Bachenheimer

2005

J Virol

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“…5) and DNA sequencing (data not shown). The viruses vCPc0 (55), which expresses the ␣0 cDNA (81), and vCM2/7 (11) have been described previously.…”

Section: Resultsmentioning

confidence: 99%

“…ICP27, another essential protein, is required for the expression of ␤ and ␥ genes during the HSV life cycle. This protein appears to act primarily at the posttranscriptional level (47,59,62,65,67,73); however, recent evidence supports a more direct role for ICP27 in the regulation of gene expression (55).…”

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confidence: 99%

“…(i) Transfection. Transfections were performed by the calcium phosphate method as described previously (55,77), with the addition of a 1-min glycerol shock with 1 ml of 15% glycerol in HEPES-buffered saline (3). All transfection mixtures contained a total of 15 g of DNA: 1 g of the indicated luciferase reporter plasmid; 0, 0.1 (data not shown), or 1 g of the indicated wild-type or mutant ␣0 cDNA; and carrier plasmid.…”

mentioning

confidence: 99%

“…Vero cells were transfected with 15 g of plasmid DNAs, as described above. 293T cells were transfected, as previously described (55), with 15 g of DNA. At 48 h posttransfection, the cells were scraped into ice-cold phosphate-buffered saline (PBS) and collected by centrifugation at 4°C.…”

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confidence: 99%

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Mutational analysis of the herpes simplex virus type 1 ICP0 C3HC4 zinc ring finger reveals a requirement for ICP0 in the expression of the essential alpha27 gene

Lium

Silverstein

1997

J Virol

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The herpes simplex virus type 1 (HSV-1) immediate-early (IE) protein ICP0 has been implicated in the regulation of viral gene expression and the reactivation of latent HSV-1. Evidence demonstrates that ICP0 is an activator of viral gene expression yet does not distinguish between a direct or indirect role in this process. To further our understanding of the function of ICP0 in the context of the virus life cycle, site-directed mutagenesis of the consensus C 3 HC 4 zinc finger domain was performed, and the effects of these mutations on the growth and replication of HSV-1 were assessed. We demonstrate that alteration of any of the consensus C 3 HC 4 cysteine or histidine residues within this domain abolishes ICP0-mediated transactivation, alters the intranuclear localization of ICP0, and significantly increases its stability. These mutations result in severe defects in the growth and DNA replication of recombinant herpesviruses and in their ability to initiate lytic infections at low multiplicities of infection. These viruses, at low multiplicities of infection, synthesize wild-type levels of the IE proteins ICP0 and ICP4 at early times postinfection yet exhibit significant decreases in the synthesis of the essential IE protein ICP27. These findings reveal a role for ICP0 in the expression of ICP27 and suggest that the multiplicity-dependent growth of ␣0 mutant viruses results partially from reduced levels of ICP27.

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Functional Domains within the Nucleus of a Cell Infected with HSV-1

Phelan

Clements

1997

Rev. Med. Virol.

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HSV‐1 is a nuclear replicating DNA virus capable of establishing both lytic and latent infections in mammalian cells. Expression of the more than 80 HSV genes (the majority of which do not contain introns) requires complex coordination of viral and cellular factors both temporally, at appropriate points during the infectious cycle, and spatially as the virus transcription, replication and DNA packaging factories develop in the cell nucleus. Whilst the HSV genome encodes sufficient proteins to sustain viral DNA replication, it is reliant upon its host cell for RNA polymerase II and RNA processing machinery, in addition to an increasing number of cellular cofactors, for gene expression. As HSV establishes a lytic infection, cellular gene expression and splicing are inhibited as cellular chromatin is displaced and a dramatic reorganisation of the host cell nucleus occurs. The formation of large protein‐rich factories synthesising viral RNA and replicating and packaging the viral genomes is the most striking alteration. In addition to the synthetic factories, large clumps of cellular and viral intron‐containing RNAs accumulate in the nucleus as a result of the inhibition of splicing, at locations which colocalise with splicing factors, but are separate from transcription sites. An essential HSV protein IE63, discussed here, has been identified with a role in the organisation of the nucleus at many levels including replication and transcription site formation, splicing factor organisation and the transport of RNA. This review is a summary of our present understanding of the organisation of the HSV infected cell nucleus, relating viral genomes, RNA, DNA and proteins in the context of the nucleus. However this is a rapidly evolving field and new factors (both viral and cellular) involved in the regulation of these functional domains are constantly being identified. © 1997 by John Wiley & Sons, Ltd.

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Physical and functional interactions between herpes simplex virus immediate-early proteins ICP4 and ICP27

Cited by 67 publications

References 100 publications

Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38

Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38

Mutational analysis of the herpes simplex virus type 1 ICP0 C3HC4 zinc ring finger reveals a requirement for ICP0 in the expression of the essential alpha27 gene

Functional Domains within the Nucleus of a Cell Infected with HSV-1

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