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

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

Sustained virological and biochemical responses to lamivudine and adefovir dipivoxil combination in a chronic hepatitis B infection despite mutations conferring resistance to both drugs.

International audienceABSTRACT: BACKGROUND: Sequential monotherapies of nucleotide analogs used in chronic hepatitis B treatment can lead to the selection of a resistance mutation to each antiviral drug. CASE PRESENTATION: A patient with chronic hepatitis B was successively treated with lamivudine monotherapy, lamivudine-adefovir dual therapy, adefovir monotherapy and again with an adefovir-lamivudine dual therapy. Lamivudine-associated mutations (rtL180M and rtM204V/I) followed by adefovir-associated mutations (rtN236T and rtA181V) emerged during the two monotherapy regimens. Despite the presence of rtM204V/I, rtA181V, and rtN236T mutations at the beginning of the second dual therapy, sustained biochemical and virological responses have been observed thus far after 23 months. CONCLUSION: This case illustrates that rtM204V/I, rtA181V, and rtN236T resistance mutations can coexist in a patient but do not preclude the recycling of lamivudine and adefovir in combination therapy, when no other therapeutic choices are available

Multicenter Evaluation of a Rapid and Convenient Method for Determination of Cytomegalovirus Immunoglobulin G Avidity

An easy, rapid, and reproducible test to distinguish residual cytomegalovirus (CMV) immunoglobulin M (IgM) antibodies from antibodies produced in primary infection could be useful, especially for pregnant women. The CMV avidity of IgG antibodies with the VIDAS automated enzyme-linked fluorescent assay and 6 M urea was evaluated in a multicenter study to differentiate between primary CMV infections and past infections or reactivations. A total of 416 serum specimens were tested: 159 specimens were from follow-up of primary infections, and 257 were from past infections. All of the specimens from primary infections collected within 4 months (17 weeks) after the onset of the infection had an avidity index lower than 0.8. An avidity index higher than 0.8 excludes a recent primary infection of less than 4 months. However, an avidity index higher than 0.8 cannot confirm all past infections, since 48 specimens (18%) from past infections had an avidity index lower than 0.8 (between 0.5 and 0.8). The exclusion capacity could be improved (96.9%) by using a cutoff of 0.7, but this index would decrease the specificity of the technique, since the avidity index was found to be between 0.7 and 0.8 in two patients with recent primary infection. All specimens from primary infections obtained more than 4 months after the onset of infection had an avidity index more than 0.2. In this study, an avidity index less than 0.2 confirms the presence of a recent primary infection of less than 4 months. The VIDAS CMV IgG avidity test is a rapid, reproducible test with very good performance