Publications of Bernard Rentier
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See detailThe role of varicella zoster virus immediate-early proteins in latency and their potential use as components of vaccines
Sadzot-Delvaux, Catherine ULiege; Rentier, Bernard ULiege

in Gershon, A. A.; Calisher, C. H.; Arvin, A. M. (Eds.) Immunity to and Prevention of Herpes Zoster (2001)

Varicella zoster virus immediate-early (IE) proteins are intracellular regulators of viral gene expression. Some of them (IE62 and IE63) are found in large amounts in infected cells but are also ... [more ▼]

Varicella zoster virus immediate-early (IE) proteins are intracellular regulators of viral gene expression. Some of them (IE62 and IE63) are found in large amounts in infected cells but are also components of the virion tegument. Several IE and early genes are transcribed during latency, while late genes are not. Recently, we demonstrated the presence of protein IE 63 in dorsal root ganglia of persistently infected rats as well as in normal human ganglia; other IE proteins have been found since in human ganglia. Cell-mediated immunity (CMI) to IE 62 has been evidenced. We found both humoral immunity and CMI to IE 63 in immune adults. In elderly zoster-free individuals, CMI to IE 63 remained high. The differences in the CMI to IE 63 among young adults, elderly people and immunocompromized patients have to be analyzed according to their status relative to zoster, to determine whether the decrease in CMI, particularly to IE proteins, could be responsible for viral reactivation and for the onset of shingles. Hopefully, the waning of the CMI to VZV IE 63 and perhaps to other IE proteins could become a predictive marker for herpes zoster and reimmunization, not only with the vaccine strain, but also with purified IE proteins could help prevent zoster at old age. [less ▲]

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See detailComment je traite une ascite
Gielen, S.; Delwaide, Jean ULiege; Detry, Olivier ULiege et al

in Revue Médicale de Liège (2001), 56(12), 809-815

Ascites is the most common of the major complications of cirrhosis. The initial evaluation of a patient with ascites should include a history, physical evaluation and some investigations. Treatment should ... [more ▼]

Ascites is the most common of the major complications of cirrhosis. The initial evaluation of a patient with ascites should include a history, physical evaluation and some investigations. Treatment should consist of treating the underlying liver disease, sodium restricted diet (2 g of Na+/day) and diuretics. This regimen is effective in 90 % of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracentesis, peritoneovenous shunting, TIPSand liver transplantation. The treatment and prophylaxis of spontaneous bacterial peritonitis which is a frequent and severe complication in cirrhotic patients with ascites is also important. The differential diagnosis with secondary bacterial peritonitisis is essential because the latter usually does not resolve unless patients are surgically treated. [less ▲]

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See detailGene activation by varicella-zoster virus IE4 protein requires its dimerization and involves both the arginine-rich sequence, the central part, and the carboxyl-terminal cysteine-rich region
Baudoux, Laurence; Defechereux, Patricia; Rentier, Bernard ULiege et al

in Journal of Biological Chemistry (2000), 275(42), 32822-32831

Varicella-zoster virus (VZV) open reading frame 4-encoded protein (IE4) possesses transactivating properties for VZV genes as well as for those of heterologous viruses. Since most transcription factors ... [more ▼]

Varicella-zoster virus (VZV) open reading frame 4-encoded protein (IE4) possesses transactivating properties for VZV genes as well as for those of heterologous viruses. Since most transcription factors act as dimers, IE4 dimerization was studied using the mammalian two-hybrid system. Introduction of mutations in the IE4 open reading frame demonstrated that both the central region and the carboxyl-terminal cysteine-rich domain were important for efficient dimerization. Within the carboxyl-terminal domain, substitution of amino acids encompassing residues 443-447 totally abolished dimerization. Gene activation by IE4 was studied by transient transfection with an IE4 expression plasmid and a reporter gene under the control of either the human immunodeficiency virus, type 1, long terminal repeat or the VZV thymidine kinase promoter. Regions of IE4 important for dimerization were also shown to be crucial for transactivation. In addition, the arginine-rich domains Rb and Re of the amino-terminal region were also demonstrated to be important for transactivation, whereas the Ra domain as well as an acidic and bZIP-containing regions were shown to be dispensable for gene transactivation. A nucleocytoplasmic shuttling of IE4 has also been characterized, involving a nuclear localization signal identified within the Rb domain and a nuclear export mechanism partially depending on Crm-1. [less ▲]

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See detailLe virus de la varicelle et du zona dans le système nerveux : retraite silencieuse ou guérilla permanente ?
Rentier, Bernard ULiege; Sadzot-Delvaux, Catherine ULiege

in Virologie (2000), 4(3), 207-216

Varicella-zoster virus is a Herpesvirus responsible for three distinct clinical features : chicken pox (varicella), shingles (herpes zoster) and post-zosterian pain (post-herpetic neuralgia). Neurological ... [more ▼]

Varicella-zoster virus is a Herpesvirus responsible for three distinct clinical features : chicken pox (varicella), shingles (herpes zoster) and post-zosterian pain (post-herpetic neuralgia). Neurological aspects of these diseases such as complications of chicken pox, viral latency in sensory gan-glia and reactivation as shingles with concurrent and at times subsequent prolonged pain, are the sequels of the invasion of the peripheral nervous system during primary infection. Prevention is achieved by vaccination with a live attenuated virus strain and therapy calls for specific antiviral agents. In many respects, VZV behaves differently from close relatives. In particular, viral latency in the nervous system is quite different from that of other Herpesviri-dae. The recent discovery of the expression and accumulation of some viral regulatory proteins during latency, although VZV latency had always been considered silent, as well as the demonstration that these proteins are immu-nogenic are opening new avenues to investigate the mechanisms of VZV latency and the immune control of VZV reactivation. [less ▲]

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See detailEvidence-Based Medicine: traitement de l'hépatite chronique C. GLEVHE. Groupe Liégeois d'Etude des Virus Hépatotropes.
Delwaide, Jean ULiege; Gerard, Christiane ULiege; Belaiche, Jacques ULiege et al

in Revue Médicale de Liège (2000), 55(5), 337-340

The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The major characteristic of virus C is its tendency to chronicity in more than 85% of cases. Generally asymptomatic, HCV ... [more ▼]

The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The major characteristic of virus C is its tendency to chronicity in more than 85% of cases. Generally asymptomatic, HCV infection may also evolve with time to cirrhosis and hepatocellular carcinoma. During the last few years, HCV-related end-stage cirrhosis has become the first cause of liver transplantation. In 10 years only, very significant progress has been made in the knowledge of the virus, not only in the field of diagnosis but also in therapy. Several consensus conferences taking last discoveries into account have been organized in order to promote recommendations useful for the management of hepatitis C patients. The aim of this short overview is to summarize practical recommendations that emerged recently from consensus meetings. [less ▲]

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See detailChronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects
Nikkels, Arjen ULiege; Snoeck, Robert; Rentier, Bernard ULiege et al

in Clinical and Experimental Dermatology (1999), 24(5), 346-353

The outbreak of HIV infection introduced a new phenomenon in varicella zoster virus (VZV) pathology, namely the long-standing wart-like skin lesions that are frequently associated with resistance to ... [more ▼]

The outbreak of HIV infection introduced a new phenomenon in varicella zoster virus (VZV) pathology, namely the long-standing wart-like skin lesions that are frequently associated with resistance to thymidine kinase (TK)-dependent antiviral agents. This paper reviews the clinical, histological, and molecular aspects and the therapeutic management of these verrucous lesions. The majority of lesions are characterized by chronically evolving, unique or multiple wart-like cutaneous lesions. The main histopathological features include hyperkeratosis, verruciform acanthosis and VZV-induced cytopathic changes with scant or absent cytolysis of infected keratinocytes. The mechanism that establishes the chronic nature of the lesions appears to be associated with a particular pattern of VZV gene expression exhibiting reduced or nondetectable gE and gB synthesis. Drug resistance to TK-dependent antiviral agents is a result of nonfunctional or deficient viral TK. This necessitates alternative therapeutic management using antiviral agents that target the viral DNA polymerase. [less ▲]

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See detailHepatitis C virus transmission following invasive medical procedures
Delwaide, Jean ULiege; Gerard, Christiane ULiege; Vaira, Dolorès ULiege et al

in Journal of Internal Medicine (1999), 245(1), 107-108

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See detailVaricella-zoster virus IE63, a virion component expressed during latency and acute infection, elicits humoral and cellular immunity
Sadzot-Delvaux, Catherine ULiege; Arvin, Ann M.; Rentier, Bernard ULiege

in Journal of Infectious Diseases (1998), 178(Suppl. 1), 43-47

Varicella-zoster virus (VZV) latency in human dorsal root ganglia is characterized by the transcription of large regions of its genome and by the expression of large amounts of some polypeptides, which ... [more ▼]

Varicella-zoster virus (VZV) latency in human dorsal root ganglia is characterized by the transcription of large regions of its genome and by the expression of large amounts of some polypeptides, which are also expressed during lytic cycles. The immediate early 63 protein (IE63) is a virion component expressed very early in cutaneous lesions and the first viral protein detected during latency. Immune response against IE63 has been evaluated among naturally immune adults with a history of chickenpox: Specific antibodies were detected in serum, and most subjects who had a T cell proliferation with unfractionated VZV antigens had T cell recognition of purified IE63. The cytotoxic T cell (CTL) response to IE63 was equivalent to CTL recognition of IE62, the major tegument component of VZV, whose immunogenicity has been previously described. T cell recognition of IE63 and other VZV proteins is one of the likely mechanisms involved in controlling VZV reactivation from latency. [less ▲]

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See detailActivation of the human immunodeficiency virus long terminal repeat by varicella-zoster virus IE4 protein requires nuclear factor-kB and involves both the amino-terminal and the carboxyl-terminal cysteine-rich region
Defechereux-Thibaut de Maisières, Patricia; Baudoux-Tebache, Laurence; Merville, Marie-Paule ULiege et al

in Journal of Biological Chemistry (1998), 273(22), 13636-13644

Varicella-zoster virus open reading frame 4-encoded protein (IE4) possesses transactivating properties for varicella-zoster virus genes as well as for those of heterologous viruses such as the human ... [more ▼]

Varicella-zoster virus open reading frame 4-encoded protein (IE4) possesses transactivating properties for varicella-zoster virus genes as well as for those of heterologous viruses such as the human immunodeficiency virus type 1 (HIV-1). Mechanisms of HIV-1 LTR (long terminal repeat) transactivation were investigated in HeLa cells transiently transfected with an IE4 expression plasmid and a CAT reporter gene under the control of the HIV-1 LTR. These results demonstrated that IE4-mediated transactivation of the HIV-1 LTR in HeLa cells required transcription factor kappaB (NF-kappaB). Using the gel retardation assay, it was shown that transfection of the IE4 expression vector in HeLa cells was not associated with induction of NF-kappaB under the p50.p65 heterodimeric form and that no direct binding of IE4 to the kappaB sites could be detected. Both Western blot and immunofluorescence analyses suggested that the ability of IE4 to activate transcription through kappaB motives was not connected with its capacity to override the inhibitory activities of IkappaB-alpha or p105. Finally, in vitro protein-protein interactions involving IE4 and basal transcription factors such as TATA-binding protein and transcription factor IIB were carried out. A direct interaction between IE4 and TATA-binding protein or transcription factor IIB components of the basal complex of transcription was evidenced, as well as binding to the p50 and p65 NF-kappaB subunits. Mutagenesis analysis of IE4 indicated that the COOH-terminal cysteine-rich and arginine-rich regions (residues 82-182) were critical for transactivation, whereas the first 81 amino acids appeared dispensable. Moreover, the arginine-rich region is required for the in vitro binding activity, whereas the COOH-terminal end did not appear essential. [less ▲]

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See detailPhysiopathologie et pathogenèse des douleurs zostériennes
Rentier, Bernard ULiege

in Médecine et Maladies Infectieuses (1998), 28(Sp. Iss), 848-850

The origin of post-zosterian pain appears to be multiple. It implies: neuronal lesions in the central and peripheral nervous system. Young patients are less often affected than older individuals, perhaps ... [more ▼]

The origin of post-zosterian pain appears to be multiple. It implies: neuronal lesions in the central and peripheral nervous system. Young patients are less often affected than older individuals, perhaps because of damages that are caused or not to central afferences. Pain could be due to a central hyperexcitability induced and maintained by nociceptors. Antagonists of the NMDA receptor could thus prove efficient against installation of the chronic pain by interfering with neuronal discharges of the peripheral nociceptors and the induction of a hyperexcitability. [less ▲]

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See detailSciences et Médecine à Liège à l'aube du troisième millénaire
Legros, Willy ULiege; Rentier, Bernard ULiege

in MS. Medecine Sciences (1998), 14(5), 535-536

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See detailTransmission du virus de l'hépatite C par examens médicaux invasifs
DELWAIDE, Jean ULiege; Gerard, Christiane ULiege; Vaira, Dolorès ULiege et al

in Gastroentérologie Clinique et Biologique (1998), 22(2), 172

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See detailLa régulation des cycles infectieux du virus de la varicelle et du zona
Piette, Jacques ULiege; Defechereux-Thibaut de Maisières, Patricia; Baudoux-Tebache, Laurence et al

in M S-Médecine Sciences (1998), 14(5), 556-565

Varicella-zoster virus (VZV) is an Alphaherpesvirus responsible for two human diseases: primary exposure to the virus results in chicken pox (varicella) and reactivation following a period of latency in ... [more ▼]

Varicella-zoster virus (VZV) is an Alphaherpesvirus responsible for two human diseases: primary exposure to the virus results in chicken pox (varicella) and reactivation following a period of latency in dorsal lia gives rise to shingles (zoster). Interestingly, several transcripts corresponding to regulatory proteins present during the lytic cycle can be found in latently infected cells. The IE62 protein, component of the viral tegument, is a nuclear phosphoprotein. IE62 may play a crucial role in triggering and regulating the replicative cycle of VZV since it transactivates all classes of VZV genes and is able to repress or activate its own promoter. Moreover, IE62 acts in synergy with IE4, another important regulatory protein, to stimulate VZV gene promoters and IE62 is responsible for the translocation of IE4 from the cytoplasm to the nucleus. IE4 is expressed at very early times of the VZV productive cycle, Predominantly localized in the cytoplasm, IE4 activates several VZV genes, either alone or in synergy with IE62, as well as heterologous viral genes. At the molecular level, IE4 seems to act both transcriptionally and post-transcriptionally. Another major VZV protein is a 45 kDa phosphorylated protein, called IE63, which is abundantly expressed at the onset of the productive cycle. It is also defected during latency in humans and in a rat animal model an unexpected observation in Alphaherpesviruses. IE63 displays little direct effect on VZV gene promoters, it shows no inhibitory effect on the transactivating functions of IE62 but it represses the IE4 mediated activation. Studies conducted to define the mode of action of three VZV regulatory proteins playing crucial roles in the latency and reactivation of the am-rus mil not only lead to a better understanding of the virus pathogenesis but will probably help define novel therapeutic tools. [less ▲]

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See detailVaricella-zoster virus open reading frame 4 encodes an immediate-early protein with posttranscriptional regulatory properties
Defechereux, Patricia; Debrus, Serge; Baudoux, Laurence et al

in Journal of Virology (1997), 71(9), 7073-7079

Varicella-zoster virus (VZV) encodes four putative immediate-early proteins based on sequence homology with herpes simplex virus type I: the products of ORF4, -61, -62, and -63. Until now, only two VZV ... [more ▼]

Varicella-zoster virus (VZV) encodes four putative immediate-early proteins based on sequence homology with herpes simplex virus type I: the products of ORF4, -61, -62, and -63. Until now, only two VZV proteins have been described as being truly expressed with immediate-early kinetics (IE62 and IE63). The ORF4-encoded protein can stimulate gene expression either alone or in synergy with the major regulatory protein IE62. Making use of a sequential combination of transcription and protein synthesis inhibitors (actinomycin D and cycloheximide, respectively), we demonstrated the immediate-early nature of the ORF4 gene product, which can thus be named IE4. The fact that IE4 is expressed with kinetics similar to that of IE62 further underlines the possible cooperation between these two VZV proteins in gene expression. Analysis of the IE4-mediated autologous or heterologous viral gene expression at the mRNA levels clearly indicated that IE4 may have several mechanisms of action. Activation of the two VZV genes tested could occur partly by a posttranscriptional mechanism, since increases in chloramphenicol acetyltransferase (CAT) mRNA levels do not account for the stimulation of CAT activity. On the other hand, stimulation of the human immunodeficiency virus type 1 long terminal repeat-or the cytomegalovirus promoter-associated CAT activity is correlated with an increase in the corresponding CAT mRNA. [less ▲]

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See detailChronic varicella-zoster virus skin lesions in patients with human immunodeficiency virus are related to decreased expression of gE and gB
Nikkels, Arjen ULiege; Rentier, Bernard ULiege; Pierard, Gérald ULiege

in Journal of Infectious Diseases (1997), 176(1), 261-264

The pathogenesis of chronic, verrucous varicella-zoster virus (VZV) cutaneous lesions in human immunodeficiency virus (HIV)-infected persons is unknown. It has been hypothesized that these lesions are due ... [more ▼]

The pathogenesis of chronic, verrucous varicella-zoster virus (VZV) cutaneous lesions in human immunodeficiency virus (HIV)-infected persons is unknown. It has been hypothesized that these lesions are due to an altered pattern of virus gene expression. Immediate early and late (L) gene expression in five chronic verrucous VZV lesions, four full-blown herpes zoster vesicular lesions in HIV-infected persons, and eight vesicular herpes zoster lesions in immunocompetent individuals was semiquantitatively assessed immunohistochemically using specific antibodies to the IE63, gE (L), and gB (L) proteins. All patients had evidence of IE63 expression in keratinocytes; however, gE expression was either weak or absent in keratinocytes of three verrucous lesions, and gB was either weak or absent in two. These results suggest that chronic VZV skin lesions are associated with diminished gE and gB expression. It is inferred that the VZV behavior in keratinocytes may vary from a latency-like state to a fully developed, productive infection. [less ▲]

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See detailLes recherches sur la biologie moléculaire du virus de la varicelle et du zona (VZV) ont-elles des applications cliniques ?
Rentier, Bernard ULiege

in Annales de Dermatologie et de Vénéréologie (1997), 124(Suppl. 2), 4-8

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See detailRecognition of the latency-associated immediate early protein IE63 of varicella-zoster virus by human memory T-lymphocytes
Sadzot-Delvaux, Catherine ULiege; Kinchington, Paul R.; Debrus, Serge et al

in Journal of Immunology (1997), 159(6), 2802-2806

Varicella-zoster virus (VZV) is a human alpha herpesvirus that establishes latency in sensory ganglia. Latency is characterized by the abundant expression of the immediate early protein 63 (IE63), whereas ... [more ▼]

Varicella-zoster virus (VZV) is a human alpha herpesvirus that establishes latency in sensory ganglia. Latency is characterized by the abundant expression of the immediate early protein 63 (IE63), whereas other viral proteins have not yet been detected during the quiescent phase of VZV infection. The IE63 protein is a component of the virion and is expressed very early in the infectious cycle. The IE63 protein is also expressed in skin during episodes of varicella and herpes zoster. We have evaluated the cell-mediated immune response against IE63 in naturally immune adults with a history of chickenpox, by T lymphoproliferation and cytotoxicity assays. Among donors who had T cell proliferation to unfractionated VZV Ags from infected cell extract, 59% had T cell recognition of purified IE63. The CTL response to IE63 was equivalent to CTL recognition of IE62, the major tegument component of VZV whose immunogenicity has been previously described. IgG Abs against IE63 were detected in serum from healthy immune adults. These results indicate that IE63 is an important target of immunity to VZV. T cell recognition of IE63 is likely to be involved in controlling VZV reactivation from latency. [less ▲]

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See detailAssessment of pain in herpes zoster: lessons learned from antiviral trials
Dworkin, R. H.; Carrington, D.; Cunningham, A. et al

in Antiviral Research (1997), 33(2), 73-85

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but ... [more ▼]

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster. [less ▲]

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