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

in Journal of General Virology (The) (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 regulation
Piette, Jacques ULg; Defechereux, Patricia; Baudoux, Laurence et al

in Neurology (1995), 45(12, suppl. 8), 23-27

The varicella-zoster virus genome contains 71 open reading frames (ORFs), five of which (ORF62, ORF4, ORF63, ORF61, and ORF10) encode regulatory proteins. ORF62 codes for the major immediate early protein ... [more ▼]

The varicella-zoster virus genome contains 71 open reading frames (ORFs), five of which (ORF62, ORF4, ORF63, ORF61, and ORF10) encode regulatory proteins. ORF62 codes for the major immediate early protein of the virus exhibiting DNA-binding and regulatory functions. This protein, localized in the cell nucleus, is a functional homologue to ICP4 of herpes simplex virus type 1 (HSV-1). It trans-activates several varicella-zoster virus promoters of the various gene classes and autoregulates its own expression. ORF4 protein activates gene promoters provided they have basal activities, but it is not a functional homologue of HSV-1 ICP27. Gene regulation activity appears to be linked to its cysteine-rich C-terminal region. ORF63 codes for an immediate early protein mainly located in the cell nucleus. The regulatory functions it performs are still unclear. ORF61 protein is the functional homologue of HSV-1 ICPO. Its N-terminal region exhibits a RING domain responsible for trans-activating and trans-repressing activities. ORF10 protein exhibits similarities with HSV-1 VP16 and activates the ORF62 promoter. [less ▲]

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See detailLocalization of varicella-zoster virus nucleic acids and proteins in human skin.
Nikkels, Arjen ULg; Debrus, S.; Sadzot-Delvaux, Catherine ULg et al

in Neurology (1995), 45(12 Suppl 8), 47-9

The pathogenic mechanisms involved in varicella-zoster virus (VZV) infections remain elusive. The pattern of cutaneous distribution of the IE63 protein and of the gpI (gE) and gpII glycoproteins with ... [more ▼]

The pathogenic mechanisms involved in varicella-zoster virus (VZV) infections remain elusive. The pattern of cutaneous distribution of the IE63 protein and of the gpI (gE) and gpII glycoproteins with their corresponding genome sequences during VZV infections was studied by immunohistochemistry and in situ hybridization. Skin biopsy specimens were obtained from immunocompetent and immunocompromised patients with varicella, herpes zoster, or atypical VZV lesions. The first evidence for VZV infection consisted of the presence of IE63 in keratinocytes. In the vesicles and pustules, the viral transcripts gpI, gpII, and IE63 and the corresponding nucleic acids for gpI and gpII were identified in keratinocytes, sebocytes, Langerhans cells, dermal dendrocytes, monocytes/macrophages, and endothelial cells. The gpI and gpII glycorpoteins were essentially located on the cellular membranes while IE63 expression was generally restricted to the nuclei. In three biopsies of early herpes zoster, viral proteins were disclosed in dermal nerves and in perineurial type I dendrocytes. This was never encountered in varicella. Vasculitic changes and endothelial cell involvement were more prominent in varicella than in herpes zoster. It is concluded that the secondary viremia in varicella that affects the dermal endothelial cells is followed by a cell-to-cell spread to keratinocytes. In herpes zoster, the viral progression through cutaneous nerves primarily extends to the pilosebaceous units with a secondary involvement of epidermal keratinocytes, followed by a further spread to dermal cells. [less ▲]

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See detailImmunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use.
Nikkels, Arjen ULg; Debrus, S.; Sadzot-Delvaux, Catherine ULg et al

in Journal of Medical Virology (1995), 47(4), 342-7

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical ... [more ▼]

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments. [less ▲]

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See detailEpithelial-to-Mesenchymal Transition in Hpv-33-Transfected Cervical Keratinocytes Is Associated with Increased Invasiveness and Expression of Gelatinase A
Gilles, Christine ULg; Polette, M.; Piette, Jacques ULg et al

in International Journal of Cancer = Journal International du Cancer (1994), 59(5), 661-6

The invasive potential of a set of HPV-33- and HPV-33 + ras-transfected cervical keratinocytes was investigated. These cell lines were previously separated into 2 groups according to their behavior on ... [more ▼]

The invasive potential of a set of HPV-33- and HPV-33 + ras-transfected cervical keratinocytes was investigated. These cell lines were previously separated into 2 groups according to their behavior on collagen rafts. Cell lines from the first group reconstituted CINIII-like lesions, whereas cell lines from the second group reconstituted epithelia comparable to micro-invasive carcinomas. They were thus postulated to represent distinct stages of cervical carcinogenesis. The present results have shown that lines from group I, which have conserved an epithelial morphology in monolayer, (i) could not invade matrigel when tested in a modified Boyden chamber assay, (ii) produced solely gelatinase B and (iii) were unable to activate exogenous gelatinase A. On the other hand, lines from group II associated epithelial-to-mesenchymal transition (acquisition of elongated morphology, vimentin positivity) with high in vitro invasive potential and with the ability both to produce and to activate gelatinase A. These results strongly support the hypothesis that the epithelial-to-mesenchymal transition and the associated events might be implicated in the progression to the metastatic phenotype. [less ▲]

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See detailVaricelle et zona: Virus VZV, étiologie, complications et traitement
Rentier, Bernard ULg; Piette, Jacques ULg; Nikkels, Arjen ULg

in Patient Care (1994), 17

La varicelle est une affection très fréquente et très contagieuse. Presque toujours bénigne chez l'enfant, elle peut être plus grave chez l'adulte. Quant au zona, il frappe essentiellement les adultes. C ... [more ▼]

La varicelle est une affection très fréquente et très contagieuse. Presque toujours bénigne chez l'enfant, elle peut être plus grave chez l'adulte. Quant au zona, il frappe essentiellement les adultes. C'est le seul et même virus de la varicelle et du zona (Varicella-Zoster Virus, VZV) qui constitue le lien commun entre les 2 maladies. Sa particularité est de fonctionner par disparition-réactivation. Le VZV appartient à la famille des Herpesviridae. Proche des autres Herpès-virus comme les virus de l'Herpes simplex (HSV-1 et HSV-2), le cytomégalovirus (CMV), le virus d'Epstein-Barr (EBV) et les Herpèsvirus humains 6 et 7 (HHV-6 et HHV-7) nouvellement décrits, il possède néanmoins certaines caractéristiques propres. [less ▲]

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See detailViral glycoproteins in herpesviridae granulomas
Nikkels, Arjen ULg; Debrus, S.; Delvenne, Philippe ULg et al

in American Journal of Dermatopathology (1994), 16(6), 588-592

Granulomatous reactions after varicella zoster virus (VZV) and herpes simplex virus (HSV) infections are rare, and their pathogenesis remains unclear. We studied by immunohistochemistry and in situ ... [more ▼]

Granulomatous reactions after varicella zoster virus (VZV) and herpes simplex virus (HSV) infections are rare, and their pathogenesis remains unclear. We studied by immunohistochemistry and in situ hybridization early granulomatous reactions after VZV and HSV infections. In the five cases studied, the VZV glycoproteins gp I and gp II were present in cells abutted to altered vessels, but the corresponding genome sequences were disclosed in similar locations in only one of these cases. In an immunocompromised patient with diffuse HSV eruption, HSV I antigens were present in cells of the reticular dermis, while viral nucleic acids were not evident. Immunophenotyping of the granulomas showed strong Mac 387 and CD68 positive labelings of macrophages/monocytes, without any involvement of Factor XIIIa-positive cells. These findings suggest that the major viral envelope glycoproteins, rather than complete viral particles could trigger granuloma formation following HSV and VZV skin infections. [less ▲]

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See detailDifferentiation Ability and Oncogenic Potential of Hpv-33- and Hpv-33 + Ras-Transfected Keratinocytes
Gilles, Christine ULg; Piette, Jacques ULg; Peter, W. et al

in International Journal of Cancer = Journal International du Cancer (1994), 58(6), 847-54

Five HPV-33-immortalized and 5 HPV-33 + ras-transfected cell lines were characterized in terms of growth in soft agar, tumorigenic potential in nude mice, p21 expression, morphology and expression of ... [more ▼]

Five HPV-33-immortalized and 5 HPV-33 + ras-transfected cell lines were characterized in terms of growth in soft agar, tumorigenic potential in nude mice, p21 expression, morphology and expression of differentiation markers in organotypic cultures. No striking differences were observed between the HPV-33-immortalized cell lines and their corresponding ras-transfected counterparts as regards their tumorigenicity in nude mice (only one cell line was able to develop tumors in nude mice) or their behavior on lifted collagen gels. However, all the ras-transfected cell lines gave rise to colonies in soft agar while only 2 HPV-33-transfected lines (CK1 and CK4) displayed this property. The 10 cell lines could be divided into 2 groups with respect to their phenotype in monolayer and in organotypic cultures. Lines from group I (CK2, 3, 5 and their ras-transfected homologous lines) shared a typical epithelial phenotype in monolayer and the ability (a) to form an epithelium similar to a CIN-III lesion and (b) to strongly express keratins K1-K10 and involucrin in organotypic cultures. On the other hand, for the lines from group II (CK1, CK4, CK1EJ7 and CK4EJ5), there was a correlation between an elongated phenotype in monolayer and the property (a) to form a structure similar to a microinvasive carcinoma and (b) to express vimentin and keratins K8-K18. These cell lines, exhibiting various transformation-associated alterations, can be considered as an in vitro model representing various stages of HPV-33-associated cervical carcinogenesis. [less ▲]

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See detailVZV ORF 4 encoded protein is an effective transactivor of gene expression and possesses distinct regulatory properties
Defechereux, Patricia; Baudoux, Laurence; Lambert, Chantal ULg et al

Conference (1994)

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See detailRegulation of Varicella-Zoster virus gene expression by the IE62 protein and mutational dissection of the IE62 protein
Baudoux, Laurence; Defechereux, Patricia; Rentier, Bernard ULg et al

Conference (1994)

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See detailMeningoradiculoneuritis due to acyclovir-resistant varicella zoster virus in an acquired immune deficiency syndrome patient
Snoeck, R.; Gérard, M.; Sadzot-Delvaux, Catherine ULg et al

in Journal of Medical Virology (1994), 42(4), 338-347

Varicella zoster virus (VZV) is recognized as one of the major viral pathogens reactivated in patients with the acquired immune deficiency syndrome (AIDS). We report the case of meningoradiculoneuritis in ... [more ▼]

Varicella zoster virus (VZV) is recognized as one of the major viral pathogens reactivated in patients with the acquired immune deficiency syndrome (AIDS). We report the case of meningoradiculoneuritis in an AIDS patient, associated with the isolation in the cerebrospinal fluid (CSF) of a thymidine kinase (TK)-deficient, acyclovir (ACV)-resistant strain of VZV. Although the virus was sensitive in vitro to phosphonoformate (PFA), the patient did not improve during PFA therapy and finally died. Several VZV strains isolated from this patient (including two isolates from the patient's CSF) were analyzed for their TK activity and subsequently the viral TK gene was sequenced showing a major deletion leading to a truncated protein. Their susceptibility to several antiviral agents including ACV, PFA, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 9-beta-D-arabinofuranosyladenine (vidarabine), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) was evaluated. All the virus strains isolated from this patient remained sensitive to HPMPA and HPMPC, pointing to the potential usefulness of these acyclic nucleoside phosphonates for the treatment of ACV-resistant VZV infections in immunocompromised patients. (C) 1994 Wiley-Liss, Inc. [less ▲]

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See detailRegulation of VZV gene expression by the IE62 protein and mutational dissection of the IE62 protein
Baudoux, Laurence; Defechereux, Patricia; Rentier, Bernard ULg et al

Conference (1994)

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See detailStimulation of glutatione-peroxidase activity decreases HIV type-1 activation after oxidative stress
Sappey, C.; Legrand, Sylvie ULg; Best-Belopmme, M. et al

in AIDS Research and Human Retroviruses (1994), 10(11), 1451-1461

Am important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) by redox-controlled signal transduction pathways. In this ... [more ▼]

Am important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) by redox-controlled signal transduction pathways. In this study, we demonstrate that selenium supplementation can effectively increase glutathione peroxidase (GPx) activity in latently infected T lymphocytes. The Se-supplemented cells exhibited an important protection against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). Concomitantly, NF-kappa B activation by H2O2 was also decreased in Se-supplemented cells. Selenium stimulation of GPx activity also induces a protective effect against cell activation by tumor necrosis factor alpha (TNF-alpha) but less significantly by phorbol esters such as PMA. These Se-mediated effects were specific because they were not found when AP-1 DNA-binding activity was studied after H2O2-induced stress. Hyperthermia was also studied because it could promote intracellular electron leakage in electron transport chains. Elevating the temperature to 42 degrees C did not induce NF-kappa B directly. Rather, it sensitized infected cells to subsequent oxidative stress by H2O2, demonstrating the importance of hyperthermia, often associated with opportunistic infections in the development of immunodeficiency. In this case, Se induced partial protection against the sensitizing effect of hyperthermia. [less ▲]

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See detailCausative role of VZV in two fatal disseminated infections
Nikkels, Arjen ULg; Debrus, S.; Sadzot-Delvaux, Catherine ULg et al

Conference (1994)

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See detailVaricelle et zona: virus VZV, étiologie, complications et traitement
Rentier, Bernard ULg; Piette, Jacques ULg; Nikkels, Arjen ULg

in Patient Care (1994), (17), 35-47

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See detailCharacterization of an in vivo model of VZV latency in the nervous system
Sadzot-Delvaux, Catherine ULg; Nikkels, Arjen ULg; Debrus, S. et al

Conference (1994)

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