Publications of Bernard Rentier
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See detailLessons to be learned from varicella-zoster virus
Rentier, Bernard ULiege; Piette, Jacques ULiege; Baudoux, Laurence et al

in Veterinary Microbiology (1996), 53(1-2), 55-66

Varicella-zoster virus (VZV) is an alphaherpesvirus responsible for two human diseases: chicken pox and shingles. The virus has a respiratory port of entry. After two successive viremias, it reaches the ... [more ▼]

Varicella-zoster virus (VZV) is an alphaherpesvirus responsible for two human diseases: chicken pox and shingles. The virus has a respiratory port of entry. After two successive viremias, it reaches the skin where it causes typical lesions. There, it penetrates the peripheral nervous system and it remains latent in dorsal root ganglia. It is still debatable whether VZV persists in neurons or in satellite cells. During latency, VZV expresses a limited set of transcripts of its immediate early (IE) and early (E) genes but no protein has been detected. Mechanisms of reactivation from ganglia have not been identified. However, dysfunction of the cellular immune system appears to be involved in this process. The cell-associated nature of VZV has made it difficult to identify a temporal order of gene expression, but there appears to be a cascade mechanism as for HSV-1. The lack of high titre cell-free virions or recombination mutants has hindered so far the understanding of VZV gene functions. Five genes, ORFs 4, 10, 61, 62, and 63 that encode regulatory proteins could be involved in VZV latency. ORF4p activates gene promoters with basal activities. ORF10p seems to activate the ORF 62 promoter. ORF61p has trans-activating and trans-repressing activities. The major IE protein ORF62p, a virion component, has DNA-binding and regulatory functions, transactivates many VZV promoters and even regulates its own expression. ORF63p is a nuclear IE protein of yet unclear regulatory functions, abundantly expressed very early in infection. We have established an animal model of VZV latency in the rat nervous system, enabling us to study the expression of viral mRNA and protein expression during latency, and yielding results similar to those found in humans. This model is beginning to shed light on the molecular events in VZV persistent infection and on the regulatory mechanisms that maintain the virus in a latent stage in nerve cells. [less ▲]

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See detailIntracellular distribution of the ORF4 gene product of varicella-zoster virus is influenced by the IE62 protein
Defechereux, Patricia; Debrus, Serge; Baudoux, Laurence et al

in Journal of General Virology (1996), 77(Part 7), 1505-1513

Varicella-zoster virus (VZV) open reading frame 4-encoded protein (IE4) possesses transactivating properties for VZV genes as well as for genes of heterologous viruses, The major regulatory immediate ... [more ▼]

Varicella-zoster virus (VZV) open reading frame 4-encoded protein (IE4) possesses transactivating properties for VZV genes as well as for genes of heterologous viruses, The major regulatory immediate-early protein of VZV (IE62) is a transactivator of VZV gene expression, In transfection assays, IE4 has been shown to enhance activation induced by IE62, To investigate the functional interactions underlying this observation, indirect immunofluorescence studies were undertaken to determine whether IE62 could influence IE4 intracellular localization in transfected cells, In single transfections, IE4 was predominantly found in cytoplasm, In cotransfection with IE62, the IE4 localization pattern was altered, with nuclear staining predominating over cytoplasmic staining, This effect was specific to the IE62 protein since the gene products of ORF63 and ORF61, which are also regulatory proteins, did not influence IE4 distribution, The use of IE62 mutants indicated that IE62 influence is independent of its transactivation function and that the integrity of regions 3 and 4 is required, IE62 remained nuclear whether IE4 was present or not, These observations underline differences in the regulation of gene expression between VZV proteins and their herpes simplex virus type 1 homologues, In infected cells, IE4 was only sometimes found to colocalize with IE62 in nuclei, This observation suggests that when all VZV proteins are present, complex interactions probably occur which could diminish the influence of IE62. [less ▲]

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See detailExpression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons
Mahalingam, Ravy; Wellish, Mary; Cohrs, Randall et al

in Proceedings of the National Academy of Sciences of the United States of America (1996), 93(5), 2122-2124

The ganglionic cell type in which varicellazoster virus (VZV) is latent in humans was analyzed by using antibodies raised against in vitro-expressed VZV open reading frame 63 protein, VZV open reading ... [more ▼]

The ganglionic cell type in which varicellazoster virus (VZV) is latent in humans was analyzed by using antibodies raised against in vitro-expressed VZV open reading frame 63 protein, VZV open reading frame 63 protein was detected exclusively in the cytoplasm of neurons of latently infected human trigeminal and thoracic ganglia. This is, to our knowledge, the first identification of a herpesvirus protein expressed during latency in the human nervous system. [less ▲]

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See detailMutational analysis of varicella-zoster virus major immediate-early protein IE62
Baudoux, Laurence; Defechereux, Patricia; Schoonbroodt, Sonia et al

in Nucleic Acids Research (1995), 23(8), 1341-1349

The varicella-zoster virus (VZV) open reading frame 62 encodes an immediate-early protein (IE62) that transactivates expression of various VZV promoters and autoregulates its own expression in transient ... [more ▼]

The varicella-zoster virus (VZV) open reading frame 62 encodes an immediate-early protein (IE62) that transactivates expression of various VZV promoters and autoregulates its own expression in transient expression assays. In Vero cells, IE62 was shown to transactivate the expression of all putative immediate-early (IE) and early (E) genes of VZV with an up-regulating effect at low intracellular concentrations. To define the functional domains involved in the regulatory properties of IE62, a large number of in-frame insertions and deletions were introduced into a plasmid-borne copy of the gene encoding IE62. Studies of the regulatory activities of the resultant mutant polypeptides in transient expression assays allowed to delineate protein regions important for repression of its own promoter and for transactivation of a VZV putative immediate-early gene (ORF61) promoter and an early gene (ORF29) promoter. This mutational analysis resulted in the identification of a new functional domain situated at the border between regions 4 and 5 which plays a crucial role in the IE62 regulatory functions. This domain turned out to be very well conserved amongst homologous alphaherpesvirus regulatory proteins and appeared to be rich in bulky hydrophobic and proline residues, similar to the proline-rich region of the CAAT box binding protein CTF-1. By immunofluorescence, a nuclear localization signal has been mapped in region 3. [less ▲]

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See detailTranscription factor NF-kB is activated by photosensitization generating oxidative DNA damages
Legrand-Poels, Sylvie ULiege; Bours, Vincent ULiege; Piret, Bernard et al

in Journal of Biological Chemistry (1995), 270(12), 6925-6934

Reactive oxygen intermediates like hydrogen peroxide (H2O2) have been shown to serve as messengers in the induction of NF-kappa B and, then, in the activation and replication of human immunodeficiency ... [more ▼]

Reactive oxygen intermediates like hydrogen peroxide (H2O2) have been shown to serve as messengers in the induction of NF-kappa B and, then, in the activation and replication of human immunodeficiency virus (HIV)-1 in human cells. Because H2O2 can be converted into the highly reactive OH. at various locations inside the cells, we started to investigate the generation of Reactive oxygen intermediates by photosensitization. This technique is based on the use of a photosensitizer which is a molecule absorbing visible light and which can be located at various sites inside the cell depending on its physicochemical properties. In this work, we used proflavine (PF), a cationic molecule having a high affinity for DNA, capable of intercalating between DNA base pairs. Upon visible light irradiation, intercalated PF molecules oxidize guanine residues and generate DNA single-strand breaks. In lymphocytes or monocytes latently infected with HIV-1 (ACH-2 or U1, respectively), this photosensitizing treatment induced a cytotoxicity, an induction of NF-kappa B, and a reactivation of HIV-1 in cells surviving the treatment. NF-kappa B induction by PF-mediated photosensitization was not affected by the presence of N-acetyl-L-cysteine while strong inhibition was recorded when the induction was triggered by H2O2 or by phorbol 12-myristate 13-acetate. Another transcription factor like AP-1 is less activated by this photosensitizing treatment. In comparison with other inducing treatments, such as phorbol 12-myristate 13-acetate or tumor necrosis factor alpha, the activation of NF-kappa B is slow, being optimal 120 min after treatment. These kinetic data were obtained by following, on the same samples, both the appearance of NF-kappa B in the nucleus and the disappearance of I kappa B-alpha in cytoplasmic extracts. These data allow us to postulate that signaling events, initiated by DNA oxidative damages, are transmitted into the cytoplasm where the inactive NF-kappa B factor is resident and allow the translocation of p50/p65 subunits of NF-kappa B to the nucleus leading to HIV-1 gene expression. [less ▲]

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See detailVaricella-zoster virus induces apoptosis in cell culture
Sadzot-Delvaux, Catherine ULiege; Thonard, P.; Schoonbroodt, Sonia et al

in Journal of General Virology (1995), 76(Pt 11), 2875-2879

Apoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus ... [more ▼]

Apoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis. [less ▲]

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See detailVaricella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency
Debrus, Serge; Sadzot-Delvaux, Catherine ULiege; Nikkels, Arjen ULiege et al

in Journal of Virology (1995), 69(5), 3240-3245

Varicella-zoster virus (VZV) gene 63 encodes a protein with a predicted molecular mass of 30.5 kDa which has amino acid similarities with the immediate-early (IE) protein 22 (ICP-22) of herpes simplex ... [more ▼]

Varicella-zoster virus (VZV) gene 63 encodes a protein with a predicted molecular mass of 30.5 kDa which has amino acid similarities with the immediate-early (IE) protein 22 (ICP-22) of herpes simplex virus type 1. In order to study the expression of this protein during lytic and latent infection, gene 63 was cloned in frame and downstream from the glutathione-S-transferase gene, expressed as a fusion protein, and purified. In VZV-infected Vero cells, antibodies directed against this protein detect two polypeptides of 45 and 38 kDa which are localized both in the cytoplasm and in the nucleus. Using a sequential combination of transcription and protein synthesis inhibitors (actinomycin D and cycloheximide, respectively), we demonstrated the immediate-early nature of this protein, which can thus be named IE63. Using a rat model of VZV latency, we showed that IE63 is heavily expressed, essentially in neurons, during latency. IE63 can also be detected in the skin of patients showing early herpes zoster symptoms. [less ▲]

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See detailHow should zoster trials be conducted?
Wood, M. J.; Balfour, Hank; Beutner, Karl et al

in Journal of Antimicrobial Chemotherapy (1995), 36(6), 1089-1101

In 1994, an international group of interested clinicians and biostatisticians met to discuss the design of clinical trials in herpes tester. They agreed that trials in herpes tester should have ... [more ▼]

In 1994, an international group of interested clinicians and biostatisticians met to discuss the design of clinical trials in herpes tester. They agreed that trials in herpes tester should have prospectively agreed definitions of all outcome measures and plans for data analysis. In immunocompetent individuals, in whom pain is the major outcome measure, trials should only include patients over the age of 50 years, and for those recruited within 72 fi of rash onset, should be designed to demonstrate superiority of any new therapy over existing antivirals. The primary endpoint should be time to cessation of pain for at least 4 weeks and, for the purposes of statistical analysis of its duration, the pain associated with herpes tester ought to be considered as a continuum. All other variables, including the incidence of post-herpetic neuralgia and effects upon quality of life should be considered as secondary end-points. Evaluation of treatment effects on primary endpoints should be based upon an intent-to-treat (ITT) analysis and subgroup analysis should be used only to support the findings of the ITT analysis. These elements of good study design should be borne in mind in the evaluation of current and future trails of antiviral drugs in herpes zoster. [less ▲]

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See detailDiagnostic de la varicelle-zona et de l’herpès: l’apport du laboratoire
Nikkels, Arjen ULiege; Rentier, Bernard ULiege

in Virologics: la Virologie du Sida au Zona (1994, April)

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See detailImmunohistochemical detection of immediate early and late phase proteins expressed during the varicella-zoster virus cycle
Nikkels, Arjen ULiege; Debrus, S.; Sadzot-Delvaux, Catherine ULiege et al

in British Journal of Dermatology. Supplement (1994), 131(44), 64

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See detailCharacterization of the regulatory functions of varicella-zoster virus open reading frame-4 gene-product
Defechereux, Patricia; Melen-Lamalle, Laurence ULiege; Baudoux, Laurence et al

in Journal of Virology (1993), 67(7), 4379-4385

Varicella-zoster virus (VZV) open reading frame 4 (ORF4) encodes a protein with a predicted molecular weight of 51,540 presenting amino acid sequence homology with the immediate-early regulatory protein ... [more ▼]

Varicella-zoster virus (VZV) open reading frame 4 (ORF4) encodes a protein with a predicted molecular weight of 51,540 presenting amino acid sequence homology with the immediate-early regulatory protein ICP27 of herpes simplex virus type 1. To investigate the regulatory properties of the ORF4 gene product, we performed a series of transient expression assays in Vero cells, using a plasmid expressing ORF4 as effector and several VZV genes and heterologous genes as targets. The VZV target plasmids contained promoter/regulatory regions from genes belonging to the three putative VZV kinetic classes fused to the chloramphenicol acetyltransferase (CAT) gene. The heterologous target plasmids consisted of promoter/regulatory regions of human cytomegalovirus, Rous sarcoma virus, and human immunodeficiency virus type 1 fused to the reporter gene. These experiments demonstrated that the ORF4 gene product activated expression of ORF62 in a dose-dependent fashion but had no effect on the expression of the three other putative immediate-early genes (ORF4, ORF61, and ORF63). When various amounts of ORF4 were transfected in the presence of early gene promoters, dose-dependent transactivation was evidenced with the thymidine kinase gene (ORF36) and the major DNA-binding protein gene (ORF29) promoters; interestingly, little activity was detected with the promoter of the DNA polymerase gene (ORF28). No activation of late gene expression, represented by the glycoprotein I and glycoprotein II genes, was seen even over a wide range of concentrations of input ORF4 plasmid. Expression of pCMVCAT, pRSVCAT, and pHIVCAT was also stimulated by the ORF4 gene product. CAT mRNA analysis showed that activation of VZV target promoters occurs at the transcriptional and/or posttranscriptional level. [less ▲]

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See detailHIV-1 promoter activation following an oxidative stress mediated by singlet oxygen
Legrand, Sylvie ULiege; Hoebeke, Maryse ULiege; Vaira, Dolorès ULiege et al

in Journal of Photochemistry and Photobiology B: Biology (1993), 17(3), 229-237

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (O-1(2)) as one of the major oxidative species. Because this oxidant can be generated either ... [more ▼]

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (O-1(2)) as one of the major oxidative species. Because this oxidant can be generated either extracellularly or intracellularly, it can cause severe damage to various biological macromolecules, even to those deeply embedded inside the cells such as DNA. Sublethal biological modifications induced by different DNA-damaging agents can promote various cellular responses initiated by the activation of various cellular genes and certain heterologous viruses. Since O-1(2) fulfils essential prerequisites for a genotoxic substance, we have examined the effects of an oxidative stress, mediated by this species, on cells harbouring a heterologous promoter-leader sequence derived from the human immunodeficiency virus type 1 (HIV-1). Our results demonstrate that HIV-1 long terminal repeat (LTR), integrated into the cellular I)NA of epithelial cells, can be transactivated following an oxidative stress mediated by O-1(2). In addition, using HIV-1 latently infected promonocytes or lymphocytes, it can be shown that virus reactivation can be induced through a sublethal dose of O-1(2) generated intracellularly. An extracellular generation of O-1(2) can promote a substantial lethal effect without HIV-1 reactivation. These data may be relevant to the understanding of the events converting a latent infection into a productive one and to the appearance of the acquired immune deficiency syndrome. [less ▲]

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See detailMeningoradiculoneuritis due to acyclovir-resistant varicella-zoster virus in a patient with aids
Snoeck, R.; Gerard, M.; Sadzot-Delvaux, Catherine ULiege et al

in Journal of Infectious Diseases (1993), 168(5), 1330-1331

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See detailVZV glycoproteins gpI and gpII are present in dermal cells without their corresponding genome
Nikkels, Arjen ULiege; Delvenne, Philippe ULiege; Debrus, S. et al

in Journal of Cutaneous Pathology (1992), 19

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See detailGranulomatous reactions following herpes-zoster contain varicella-zoster glycoprotein GPI
Nikkels, Arjen ULiege; Sadzot-Delvaux, Catherine ULiege; Cloes, Jean-Michel et al

in Journal of Investigative Dermatology (1992), 98(4), 522

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See detailAntibodies to varicella-zoster virus modulate antigen distribution but fail to induce viral persistence in vitro.
Sadzot-Delvaux, Catherine ULiege; Marc, Philippe; Lebon, Linda et al

in Journal of Virology (1992), 66(12), 7499-504

Varicella-zoster virus (VZV) persists in human sensory ganglia. One of the hypotheses to explain the induction or the maintenance of VZV latency is that it could be promoted by the immune response itself ... [more ▼]

Varicella-zoster virus (VZV) persists in human sensory ganglia. One of the hypotheses to explain the induction or the maintenance of VZV latency is that it could be promoted by the immune response itself. It is known that in the case of viruses which bud off the infected cell membrane, virus-specific antibodies can induce antigenic modulation, i.e., spatial redistribution of viral antigens and modulation of their synthesis. To determine whether antigenic modulation occurs during VZV infection in vitro and could possibly be involved in viral persistence, we have grown infected cells in the presence of anti-VZV antibodies either transiently or permanently. The distribution of immune complexes and viral proteins was then analyzed. In transient immunomodulation experiments, the distribution of one or more viral antigens was modified not only in the cytoplasmic membranes but also in the cytoplasm and nucleoplasm of infected cells. When infected cells were kept permanently in the presence of antibodies, the same pattern of redistribution of immune complexes was observed and the localization of internal viral glycoproteins was significantly modified. However, antibodies did not prevent the lytic effect of infection; they altered neither the infectious virus yield nor the Western immunoblot pattern of viral proteins, suggesting that immunomodulation is not the primary effector of viral persistence. [less ▲]

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See detailCharacterization of regulatory functions of the varicella-zoster virus gene-63-encoded protein
Jackers, Pascale ULiege; Defechereux, Patricia; Baudoux, Laurence et al

in Journal of Virology (1992), 66(6), 3899-3903

Varicella-zoster virus (VZV) gene 63 encodes a protein (IE63) with a predicted molecular mass of 30.5 kDa which has amino acid similarities to the immediate-early (IE) protein 22 (ICP22) of herpes simplex ... [more ▼]

Varicella-zoster virus (VZV) gene 63 encodes a protein (IE63) with a predicted molecular mass of 30.5 kDa which has amino acid similarities to the immediate-early (IE) protein 22 (ICP22) of herpes simplex virus type 1. ICP22 is a polypeptide synthesized in herpes simplex virus type 1-infected cells, and as is the case for its VZV counterpart, its regulatory functions are unknown. On the basis of the VZV DNA sequence, it has been shown that IE63 exhibits hydrophilic and acidic properties, suggesting that this protein could play a regulatory role during the infectious cycle. We report in this article cotransfection experiments which demonstrate that the VZV gene 63 protein strongly represses, in a dose-dependent manner, the expression of VZV gene 62. On the other hand, transient expression of the VZV gene 63 protein can promote activation of the thymidine kinase gene but cannot affect the expression of the genes encoding glycoproteins I and II. The results of transient expression experiments strongly suggest that the VZV gene 63 protein could play a pivotal role in the repression of IE gene expression as well as in the activation of early gene expression [less ▲]

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See detailParasite communities: Patterns and Processes
Rentier, Bernard ULiege

in Book Reviews, Biochemical Systematics and Ecology (G. Esch, A. Bush & J. Aho, eds., Chapman & Hall, 1990) (1991)

Book review

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See detailTyping of human papillomaviruses in genital specimens by DNA hybridization
Lauricella, M.-A.; Piette, Jacques ULiege; Lifrange, Eric ULiege et al

in Archives Internationales de Physiologie et de Biochimie (1990), 98(2), 34

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See detailAbsence of seroconversion in a PCR positive person 18 months after transfusion of HIV infected blood
Vaira, Dolorès ULiege; François-Gérard, C.; Rentier, Bernard ULiege et al

in Vox Sanguinis (1989), 57(3), 220-221

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