Varicella is a common viral disease affecting almost the entire birth cohort. Although usually selflimiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete.In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all.In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella

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. Varicella-zoster virus (VZV) is an exclusively human herpesvirus that causes childhood chickenpox (varicella), becomes latent in dorsal root ganglia, and frequently reactivates decades later to produce shingles (zoster), mostly in the elderly. Unlike latent herpes simplex virus (HSV), VZV cannot be rescued by explantation or cocultivation of ganglionic cells with indicator cells in vitro. Nevertheless, postmortem analysis of latently infected sensory ganglia at all levels of the neuraxis revealed low levels of virus DNA (1) from multiple regions of the VZV genome in most humans (2, 3), including transcripts from no less than three regions of the VZV genome (4-6). Analysis of latently infected ganglia by in situ hybridization has identified VZV nucleic acid in neurons (7,8), including ganglionic neurons in an animal model of VZV latency (9, 10), and in satellite cells (4, 11). The latter finding was surprising, since VZV DNA is not integrated into cell DNA (12). Thus, the biology of VZV latency and reactivation is best explained by virus residing in and reactivating from nondividing neurons. Since antibodies against in vitro expressed product of VZV open reading frame (ORF) 63 were successfully used to detect viral antigen in rat ganglia (13) METHODSTissue Samples. One trigeminal and multiple thoracic ganglia from nine adults and three infants were obtained within 24 hr after death. None of the subjects was immunocompromised before death, and at autopsy there were no cutaneous signs of recent herpesvirus infection. The tissue samples were paraformaldehyde-fixed and paraffin-embedded. Sections (5 /-tm) were deparaffinized with 100% xylene for 5 min followed by 100% ethanol for 5 min. The xylene-alcohol treatment was repeated twice.Immunohistochemistry. Unless indicated otherwise, all incubations were at room temperature. The deparaffinized sections were incubated with a 10% (vol/vol) solution of normal sheep serum for 1 hr followed by a 1:100 dilution of either rabbit antiserum directed against the VZV ORF 63 protein (13) or normal rabbit serum (NRS) in phosphate-The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. buffered saline (PBS) for 30 min. Both rabbit sera had been preabsorbed with normal human liver powder for 30 min and again for 20 hr at 4°C. Sections were rinsed with PBS, incubated for 20 min with a 1:300 dilution of biotinylated goat anti-rabbit IgG (DAKO) in PBS containing 5% NSS, wa...

A 73-year-old man developed an ill-defined fatal vasculitis involving the central nervous system. The case report was published as a clinicopathologic exercise in February 1995 in The New England Journal of Medicine. We restudied the pathologic material and found both varicella zoster virus (VZV) DNA and VZV-specific antigen, but not herpes simplex virus (HSV) or cytomegalovirus (CMV) DNA or HSV- or CMV-specific antigen, in three of the five cerebral arteries examined. The inflammatory response, disruption of the internal elastic lamina, and detection of viral antigen were patchy from one artery to another, as well as within a given artery. A search for VZV should be conducted in cases of vasculitis when both the central and peripheral nervous systems are involved, when focal narrowing is present in large arteries, when brain imaging reveals infarction in gray and white matter, both deep and superficial, and when white matter is disproportionally involved. Zosteriform rash is not required for diagnosis.

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 posttranscriptional level.

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.