The varicella-zoster virus immediate-early 63 protein affects chromatin-controlled gene transcription in a cell-type dependent manner.
BACKGROUND
Varicella Zoster Virus Immediate Early 63 protein (IE63) has been shown to be essential for VZV replication, and critical for latency establishment. The activity of the protein as a transcriptional regulator is not fully clear yet. Using transient transfection assays, IE63 has been shown to repress viral and cellular promoters containing typical TATA boxes by interacting with general transcription factors.


RESULTS
In this paper, IE63 regulation properties on endogenous gene expression were evaluated using an oligonucleotide-based micro-array approach. We found that IE63 modulates the transcription of only a few genes in HeLa cells including genes implicated in transcription or immunity. Furthermore, we showed that this effect is mediated by a modification of RNA POL II binding on the promoters tested and that IE63 phosphorylation was essential for these effects. In MeWo cells, the number of genes whose transcription was modified by IE63 was somewhat higher, including genes implicated in signal transduction, transcription, immunity, and heat-shock signalling. While IE63 did not modify the basal expression of several NF-kappaB dependent genes such as IL-8, ICAM-1, and IkappaBalpha, it modulates transcription of these genes upon TNFalpha induction. This effect was obviously correlated with the amount of p65 binding to the promoter of these genes and with histone H3 acetylation and HDAC-3 removal.


CONCLUSIONS
While IE63 only affected transcription of a small number of cellular genes, it interfered with the TNF-inducibility of several NF-kappaB dependent genes by the accelerated resynthesis of the inhibitor IkappaBalpha.
Habran
Lionel
L
Virology & Immunology Unit, GIGA-Research, GIGA B34, University of Liège, B-4000 Liège, Belgium. lionel@habran.be
El Mjiyad
Nadia
N
Di Valentin
Emmanuel
E
Sadzot-Delvaux
Catherine
C
Bontems
Sébastien
S
Piette
Jacques
J
D002460:Cell Line / Q000187:drug effects / Q000821:virology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000821:virology; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early; D006367:HeLa Cells / Q000187:drug effects / Q000821:virology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis* / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008545:Melanoma / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D017735:Virus Latency
D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D007378:Interleukins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; C074551:immediate early protein 63, Human herpesvirus 3; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D012319:RNA Polymerase II