Characterization of an in vivo model of Varicella-Zoster (VZV) latency in the nervous system

Poster (1994, July)

Meningoradiculoneuritis due to acyclovir-resistant varicella zoster virus in an acquired immune deficiency syndrome patient

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 ▲]

Stimulation of glutatione-peroxidase activity decreases HIV type-1 activation after oxidative stress

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 ▲]

Varicelle et zona: virus VZV, étiologie, complications et traitement

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

The molecular characterization of VZV latency in the rat nervous system: a model for anti-VZV chemotherapy

Conference (1994)

Characterization of the regulatory functions of varicella-zoster virus open reading frame-4 gene-product

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 ▲]

Immortalization of Human Cervical Keratinocytes by Human Papillomavirus Type 33

in International Journal of Cancer = Journal International du Cancer (1993), 53(5), 872-9

Ten immortalized cell lines were established by transfection of human cervical keratinocytes (CK) with HPV-33 DNA and some of their characteristics were investigated. The following observations were made ... [more ▼]

Ten immortalized cell lines were established by transfection of human cervical keratinocytes (CK) with HPV-33 DNA and some of their characteristics were investigated. The following observations were made: (a) several cell lines have reached over 100 population doublings in vitro; (b) 3 transcripts were observed, 2 being encoded by the E6/E7 open reading frames (ORFs); (c) cytogenetic analyses showed important genetic modifications such as aneuploidy and isochromosome formation of the q arm of chromosome 8; (d) 2 of the 10 cell lines developed colonies in soft agar but none was able to form tumors when injected s.c. into nude mice; (e) Southern analysis suggested that a single copy of HPV-33 is integrated at a single common site within the genome of the 10 cell lines. These immortalized cell lines should be useful for studying mechanisms involved in proliferation, differentiation and neoplastic transformation of CK by HPV-33. [less ▲]

Comparative immunohistochemical study of herpes-simplex and varicella-zoster infections

in Virchows Archiv. A : Pathological Anatomy and Histopathology (1993), 422(2), 121-126

Herpes simplex (HSV) and varicella-zoster (VZV) skin infections share so many histological similarities that distinguishing between them may prove to be impossible. We developed and characterized a new ... [more ▼]

Herpes simplex (HSV) and varicella-zoster (VZV) skin infections share so many histological similarities that distinguishing between them may prove to be impossible. We developed and characterized a new monoclonal antibody, VL8, IgG kappa isotype, directed to the VZV envelope glycoprotein gpI. Immunohistochemistry with VL8 appeared highly sensitive and specific on formalin-fixed paraffin-embedded biopsies and a clear-cut distinction between HSV and VZV infections was possible. The pattern of VL8 immunolabelling in VZV infections was strikingly different from that found in HSV infections studied with polyclonal antibodies to HSV I and II. Double immunolabelling revealed the VL8 positivity of sebaceous cells, endothelial cells, Mac 387-and CD68-positive monocyte-macrophages, and factor XIIIa-positive perivascular, perineural and interstitial dendrocytes. Intracytoplasmic VL8 labelling of endothelial cells and perivascular dendrocytes was found at the site of leukocytoclastic vasculitis. [less ▲]

Meningoradiculoneuritis due to acyclovir-resistant varicella-zoster virus in a patient with aids

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

Singlet Oxygen Quantum Yield of Sulfur and Selenium Analogs of Psoralen

in Photochemistry and Photobiology (1992), 56(3), 409-412

The quantum yield of singlet oxygen production by eight newly synthesized sulfur and selenium analogs of psoralen irradiated with UV-A (366 nm) has been determined in CCl4 with the help of the steady ... [more ▼]

The quantum yield of singlet oxygen production by eight newly synthesized sulfur and selenium analogs of psoralen irradiated with UV-A (366 nm) has been determined in CCl4 with the help of the steady state luminescence technique. The new psoralen derivatives are generally better singlet oxygen producers than psoralen itself. In particular, the replacement of selenophene for furan and/or of thiopyrone for pyrone induces an important enhancement of the singlet oxygen quantum yield. [less ▲]