Phosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity

in Journal of Biological Chemistry (2002), 277(23), 21050-21060

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 ... [more ▼]

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 post-transcriptional level. [less ▲]

Cellular localization and regulatory properties of VZV Immediate early proteins in neuronal and non-neuronal cells.

Poster (2001, July)

Comment je traite une ascite

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 ▲]

Pros and cons of universal varicella vaccination in Europe : the Eurovar initiative

Poster (2001)

Importance de la phosphorylation de la protéine IE63 du virus de la varicelle et di zona (VZV) sur sa localisation et son activité

Poster (2001)

Gene activation by Varicella-zoster virus IE4 protein requires its diminution and involves both the arginine-rich sequence, the central part and the carboxy-terminal cycteine-rich region.

Poster (2000, July)

Le virus de la varicelle et du zona dans le système nerveux : retraite silencieuse ou guérilla permanente ?

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 ▲]

Chronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects

in Clinical & 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 ▲]

Overview of the replication cycle of varicella-zoster virus

in Schmidt, A.; Wolff, M. H.; Schünemann, S. (Eds.) Varicella-Zoster Virus : Molecular Biology, Pathogenesis and Clinical Aspects (1999)

La transmission du virus de l’hépatite C en milieu hospitalier

in Médecine et Hygiène (1999), 57