Enhancement of varicella-zoster virus infection in cell lines expressing ORF4- or ORF62-encoded proteins

Schoonbroodt, Stéphanie; Piette, Jacques; Baudoux, Laurence; Defechereux, Patricia; Rentier, Bernard; Merville, Marie‐Paule

doi:10.1002/(sici)1096-9071(199608)49:4<264::aid-jmv2>3.0.co;2-1

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…High levels of IE62 are associated with viral tegument (24) and a recombinant HSV-1 with both copies of ICP4 replaced by VZV IE62 has been constructed (11). IE62 can transactivate all three putative kinetic classes of VZV gene promoters-i.e., the IE, early, and late gene promoters (5,10,15,16,22,38,47,52)-and can transrepress its own promoter (5,12,49). Production of infectious VZV generated by the transfection of purified viral DNA is strongly increased by the addition of an IE62-expressing plasmid, and it has been hypothesized that virion-associated IE62 may play a crucial role in stimulating the IE events upon infection (44).…”

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confidence: 99%

Comparison of the Complete DNA Sequences of the Oka Varicella Vaccine and Its Parental Virus

Gomi

Sunamachi

Mori

et al. 2002

J Virol

173

179

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The DNA sequences of the Oka varicella vaccine virus (V-Oka) and its parental virus (P-Oka) were completed. Comparison of the sequences revealed 42 base substitutions, which led to 20 amino acid conversions and length differences in tandem repeat regions (R1, R3, and R4) and in an origin of DNA replication. Amino acid substitutions existed in open reading frames (ORFs) 6, 9A, 10, 21, 31, 39, 50, 52, 55, 59, 62, and 64. Of these, 15 base substitutions, leading to eight amino acid substitutions, were in the gene 62 region alone. Further DNA sequence analysis showed that these substitutions were specific for V-Oka and were not present in nine clinical isolates. The immediate-early gene 62 product (IE62) of P-Oka had stronger transactivational activity than the mutant IE62 contained in V-Oka in 293 and CV-1 cells. An infectious center assay of a plaque-purified clone (S7-01) from the V-Oka with 8 amino acid substitutions in ORF 62 showed smaller plaque formation and less-efficient virus-spreading activity than did P-Oka in human embryonic lung cells. Another clone (S-13) with only five substitutions in ORF 62 spread slightly faster than S7-01 but not as effectively as P-Oka. Moreover, transient luciferase assay in 293 cells showed that transactivational activities of IE62s of S7-01 and S7-13 were lower than that of P-Oka. Based on these results, it appears that amino acid substitutions in ORF 62 are responsible for virus growth and spreading from infected to uninfected cells. Furthermore, the Oka vaccine virus was completely distinguishable from P-Oka and 54 clinical isolates by seven restriction-enzyme fragment length polymorphisms that detected differences in the DNA sequence.Varicella-zoster virus (VZV) is a human herpesvirus that causes chickenpox (varicella) and shingles (herpes zoster). A live attenuated varicella vaccine, the Oka strain was originally developed by Takahashi et al. in Japan (56) and is routinely used in children in Japan and other countries, including the United States. Clinical symptoms caused by this live vaccine are very rare in healthy children. Although the Oka vaccine virus (V-Oka) is an avirulent virus, its parental virus (P-Oka), isolated from a patient with typical varicella, is thought to be virulent in vivo. It has not been clarified which gene(s) is involved in the pathogenicity of VZV infection. Thus, comparison of the complete genomes of V-Oka and P-Oka should reveal correlations between DNA sequence and virulence.The complete DNA sequence of the VZV Dumas strain was first determined by Davison and Scott (9). The genome is a linear double-stranded DNA of ca. 125,000 bp and consists of unique long regions (ULs) flanked by terminal repeat long (TRL) and internal repeat long (IRL) inverted repeat regions, and a unique short (US) region flanked by internal repeat short (IRS) and terminal repeat short (TRS) inverted repeat regions. The genome contains ca. 70 open reading frames (ORFs), three of which exist in both IRS and TRS regions; genes 62 through 64 correspond to genes 69 throug...

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confidence: 99%

Comparison of the Complete DNA Sequences of the Oka Varicella Vaccine and Its Parental Virus

Gomi

Sunamachi

Mori

et al. 2002

J Virol

173

179

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“…They were grown in RPMI 1640 (BioWhittaker) supplemented with 5% fetal bovine serum (Invitrogen). Cell-free virus was prepared from VZV-infected Mewo cells, as described previously (29). Briefly, VZV-infected Mewo cells were collected by scraping and resuspended in 1 ml of PGSA buffer supplemented with 10% fetal calf serum (29).…”

Section: Methodsmentioning

confidence: 99%

“…Cell-free virus was prepared from VZV-infected Mewo cells, as described previously (29). Briefly, VZV-infected Mewo cells were collected by scraping and resuspended in 1 ml of PGSA buffer supplemented with 10% fetal calf serum (29). Cells were mixed with 1 ml of glass beads (1 mm in diameter) and subjected to mechanical shaking in a mini-BeadBeater (Biospec Products, Bartlesville, OK), at low speed for 10 s. Supernatant containing the cell-free virus was collected by several centrifugations.…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation of Varicella-Zoster Virus IE63 Protein by Casein Kinases Influences Its Cellular Localization and Gene Regulation Activity

Bontems¹,

Valentin²,

Baudoux

et al. 2002

Journal of Biological Chemistry

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During the early phase of varicella-zoster virus (VZV) infection, Immediate Early protein 63 (IE63) is expressed rapidly and abundantly in the nucleus, while during latency, this protein is confined mostly to the cytoplasm. Because phosphorylation is known to regulate many cellular events, we investigated the importance of this modification on the cellular localization of IE63 and on its regulatory properties. We demonstrate here that cellular casein kinases I and II are implicated in the in vitro and in vivo phosphorylation of IE63. A mutational approach also indicated that phosphorylation of the protein is important for its correct cellular localization in a cell type-dependent fashion. Using an activity test, we demonstrated that IE63 was able to repress the gene expression driven by two VZV promoters and that phosphorylation of the protein was required for its full repressive properties. Finally, we showed that IE63 was capable of exerting its repressive activity in the cytoplasm, as well as in the nucleus, suggesting a regulation at the transcriptional and/or posttranscriptional level.

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“…The phosphorylation by CK2 can affect transcription factors by changing the DNA-binding activity as it is observed for c-Jun 25 and Sp1, 26 by modulating their transcriptional activities such as for MyoD, 27 HIV-1, 22 or IRF-1, 28 and by affecting protein stability, as observed for IjBa, 29,30 PTEN 31 and connexin 45.6. 32 In this work, by using classical selective inhibitors of this kinase such as apigenin, [33][34][35][36] DRB (5,6-dichloro-1-b-D-ribofuranosylbenzimidazole) 22,37,38 and TBB (4,5,6,7-tetrabromobenzotriazole), [39][40][41] we investigated the effect of hypoxia on CK2 activity and the role that this kinase may play to regulate HIF-1 activity.…”

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Role for casein kinase 2 in the regulation of HIF‐1 activity

Mottet

Ruys

Demazy

et al. 2005

Intl Journal of Cancer

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Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that plays a major role in cellular adaptation to hypoxia. The mechanisms regulating HIF-1 activity occurs at multiple levels in vivo. The HIF-1a subunit is highly sensible to oxygen and is rapidly degraded by the proteasome 26S in normoxia. Activation in hypoxia occurs through a multistep process including inhibition of HIF-1a degradation, but also increase in the transactivation activity of HIF-1. Several data indicate that phosphorylation could play a role in this regulation. In this report, we investigated the role of casein kinase 2 (CK2), an ubiquitous serine/ threonine kinase, in the regulation of HIF-1 activity. Hypoxia was capable of increasing the expression of the b subunit of CK2, of inducing a relocalization of this subunit at the plasma membrane, of inducing nuclear translocation of the a subunit and of increasing CK2 activity. Three inhibitors of this kinase, DRB (5,6-dichloro-1-b-D-ribofuranosyl-benzimidazole), TBB (4,5,6,7-tetrabromotriazole) and apigenin, as well as overexpression of a partial dominant negative mutant of CK2a, were shown to inhibit HIF-1 activity as measured by a reporter assay and through hypoxiainduced VEGF and aldolase expression. This does not occur at the stabilization process since they did not affect HIF-1a protein level. DNA-binding activity was also not inhibited. We conclude that CK2 is an important regulator of HIF-1 transcriptional activity but the mechanism of this regulation remains to be determined. Since HIF-1 plays a major role in tumor angiogenesis and since CK2 has been described to be overexpressed in tumor cells, this new pathway of regulation can be one more way for tumor cells to survive. ' 2005 Wiley-Liss, Inc.Key words: casein kinase 2; HIF-1; neoangiogenesis HIF-1 (hypoxia-inducible factor-1) is a key regulator of cell response to reduced oxygen level. In response to hypoxic conditions, HIF-1 increases the expression of downstream target genes such as erythropoietin (EPO), vascular endothelial growth factor (VEGF) and glycolytic enzymes (aldolase A, enolase-a) and mediates adaptation of cells to decreased oxygen level. 1 The role of HIF-1 in the regulation of tumor growth by hypoxia via the initiation of angiogenesis is certainly the best example of such an adaptive response. 2 Oncogene activation and tumor-suppressor inactivation result in deregulated cellular proliferation. However, most tumors grown larger than 1 mm 3 contain regions of low oxygen tension (hypoxia) due to an imbalance between oxygen supply and consumption. Formation of new blood vessels or ''neoangiogenesis'' is thus essential for further tumor growth. It is also important to allow tumor cell dissemination at distant sites, i.e., metastasis.Several studies using HIF-1 mutant cells have shown that HIF-1 has a profound effect on tumor biology. For example, tumors grown from HIF-1a-defective embryonic stem cells display abnormal vascularity and reduced growth rate. 3 Moreover, HIF-1 is upregulated in a broad r...

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Enhancement of varicella-zoster virus infection in cell lines expressing ORF4- or ORF62-encoded proteins

Cited by 8 publications

References 23 publications

Comparison of the Complete DNA Sequences of the Oka Varicella Vaccine and Its Parental Virus

Comparison of the Complete DNA Sequences of the Oka Varicella Vaccine and Its Parental Virus

Phosphorylation of Varicella-Zoster Virus IE63 Protein by Casein Kinases Influences Its Cellular Localization and Gene Regulation Activity

Role for casein kinase 2 in the regulation of HIF‐1 activity

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