Herpes-Virus Infection in Patients with Langerhans Cell Histiocytosis: A Case-Controlled Sero-Epidemiological Study, and In Situ Analysis

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that affects mainly young children, and which features granulomas containing Langerhans-type dendritic cells. The role of several human herpesviruses (HHV) in the pathogenesis of LCH was suggested by numerous reports but remains debated. Epstein-barr virus (EBV, HHV-4), & Cytomegalovirus (CMV, HHV-5) can infect Langerhans cells, and EBV, CMV and HHV-6 have been proposed to be associated with LCH based on the detection of these viruses in clinical samples. METHODOLOGY: We have investigated the prevalence of EBV, CMV and HHV-6 infection, the characters of antibody response and the plasma viral load in a cohort of 83 patients and 236 age-matched controls, and the presence and cellular localization of the viruses in LCH tissue samples from 19 patients. PRINCIPAL FINDINGS: The results show that prevalence, serological titers, and viral load for EBV, CMV and HHV-6 did not differ between patients and controls. EBV was found by PCR in tumoral sample from 3/19 patients, however, EBV small RNAs EBERs -when positive-, were detected by in situ double staining in bystander B CD20+ CD79a+ lymphocytes and not in CD1a+ LC. HHV-6 genome was detected in the biopsies of 5/19 patients with low copy number and viral Ag could not be detected in biopsies. CMV was not detected by PCR in this series. CONCLUSIONS/SIGNIFICANCE: Therefore, our findings do not support the hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans cell histiocytosis is accounted for by the infection of bystander B lymphocytes in LCH granuloma. The latter observation can be attributed to the immunosuppressive micro environment found in LCH granuloma

Evaluation par PCR de l'activité antivirale des inhibiteurs de l'ADN polymérase du Virus d'Epstein-Barr

Un système d'évaluation in vitro de l'activité de médicaments anti-EBV a été mis au point en utilisant la PCR/RT-PCR quantitative en temps réel. Trois composés appartenant à différentes classes antivirales ont été testés : un analogue nucléosidique, le ganciclovir (GCV), un analogue nucléotidique, le cidofovir (HPMPC), et un analogue du pyrophosphate, le foscarnet (PFA). Après 7 jours de traitement des cellules P3HR-1 productrices de virions, les concentrations inhibant de 50 % la réplication de l'ADN viral sont respectivement de 0.28 g/mL, 0.29 g/mL et 13.6 g/mL pour le GCV, le HPMPC et le PFA. L'expression de l'ARNm de la glycoprotéine tardive gp350/220 est réduite de 79 à 89 % après 4 jours. Nous avons aussi démontré la spécificité de l'effet antiviral en mesurant les taux d'ADN (b-globine) ou d'ARN (hPBGD) cellulaires. En conclusion, notre système permet l'évaluation de l'effet antiviral contre l'EBV de façon quantitative, simple et précise.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Caractérisation moléculaire du virus d'Epstein-Barr au décours de la mononucléose infectieuse (étude prospective)

GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Infections due to the human herpes-viruses in southern India: a seroepidemiological survey

We studied the prevalence of lgG and IgM antibodies to the human herpesviruses in a hospital-based population of 181 individuals aged 0 to 25 years, who were resident in Vellore, south India or surrounding rural areas. Antibodies to the Epstein-Barr virus (EBV) viral capsid antigen were determined by indirect immunofluorescence, while antibodies to the remaining herpesviruses were determined by enzyme-linked immunosorbent assay. The age-specific prevalence rates of IgG antibodies to EBV and cytomegalovirus (CMV) rose rapidly after birth to reach a value of over 90% by the fourth year of life. High age-specific IgM prevalence rates and geometric mean titres (GMT) of IgG antibody in children 6 months to 2 years of age, and the early median age of virus infection (1.4 years for EBV and <1 year for CMV) indicate that primary infection with these viruses occurs early in life. In contrast, age-specific prevalence rates of IgG antibodies to varicella-zoster virus (VZV) and herpes simplex virus (HSV) rose gradually after birth to attain maximal values of only 72% (VZV) and 83% (HSV) in the 15-25 year age group, and the median ages of infection were delayed (12.25 years for VZV and 8.2 years for HSV). The age-specific IgG prevalence rates of VZV and HSV, and of EBV and HSV showed statistically significant positive correlations, suggesting that common epidemiological factors may underlie the pattern of infections due to these groups of viruses. The results of this study provide baseline information on the epidemiology of human herpesvirus infections in a tropical developing country and indicate that they are common and likely to be important causes of morbidity over a wide range of ages. The clinical correlates and importance of these infections in age groups at high risk require further investigation in developing countries

Blood Monocytes Infected In Vivo by HIV-1 Variants with a Syncytium-Inducing Phenotype

International audienc

Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients.

Here we report a unique situation in which an early and synchronized Epstein-Barr virus (EBV) reactivation was induced by a 6-day course of treatment with a humanized CD3-specific monoclonal antibody in patients with recent onset of type 1 diabetes. The virologic and immunologic analysis demonstrated that this reactivation was transient, self-limited, and isolated, associated with the rapid advent of an EBV-specific T-cell response. The anti-CD3 antibody administration induced short-lasting immunosuppression and minor yet clear-cut signs of T-cell activation that preceded viral reactivation. Early posttransplant monitoring of renal and islet allograft recipients showed that no comparable phenomenon was observed after the administration of full-dose immunosuppressive therapy. This EBV reactivation remains of no apparent clinical concern over the long term and should not preclude further development of therapeutic anti-CD3 antibodies. This phenomenon may also direct new research avenues to understand the still ill-defined nature of stimuli triggering EBV reactivation in vivo.Clinical Trial, Phase IIJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe