Automated quantification of Epstein-Barr virus in whole blood for post-transplant lymphoproliferative disorders monitoring.

Background: Standardized and sensitive assays for Epstein Barr Virus (EBV) are needed to define universal cutoff for treatment initiation in allogeneic hematopoietic stem cells transplant recipients. In a context of accreditation and the availability of EBV international standard, we evaluated the Abbott RealTime EBV (RT) assay for EBV quantification in whole blood.

Methods: The RT assay was compared on 282 prospective clinical samples with the Artus EBV PCR Kit V1 assay (V1) and we analyzed the kinetics of EBV load in 11 patients receiving rituximab treatment.

Multimodal techniques failed to detect cytomegalovirus in human glioblastoma samples.

The role of the human cytomegalovirus (HCMV) in gliomagenesis is largely debated. Contradictory data exist regarding the sensitivity and specificity of HCMV detection techniques, including immunohistochemistry (IHC), in situ hybridization (ISH), and RNA and DNA sequencing. The aim of this study is to detect HCMV in glioblastoma (GBM) tumor samples using IHC, ISH, and real-time PCR (qPCR), as well as to correlate the findings with serological status and HCMV DNA load in blood.

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM.

Background: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background.

Methods: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains.

Contrasting effect of new HCMV pUL54 mutations on antiviral drug susceptibility: Benefits and limits of 3D analysis.

Human cytomegalovirus (HCMV) resistance to antiviral drugs is a major drawback of repeated or long-duration treatment in immunocompromised patients. Resistance testing is usually performed by genotypic assays. For accurate interpretation of these assays, the role of new mutations in HCMV resistance has to be assessed.

Response to antiviral therapy in haematopoietic stem cell transplant recipients with cytomegalovirus (CMV) reactivation according to the donor CMV serological status.

Pre-emptive antiviral treatment efficiently prevents occurrence of cytomegalovirus (CMV) disease in allogeneic stem cell transplant recipients. However, successive treatment courses can be necessary. The current study was aimed at determining factors that could influence the response to antiviral treatment, in particular the donor CMV serostatus.

Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T cells. We prospectively investigated natural killer-cell reconstitution in a cohort of 439 adult recipients who underwent non-T-cell-depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012.

Untreated highly viraemic pregnant women from Asia or sub-Saharan Africa often transmit hepatitis B virus despite serovaccination to newborns.

Background & Aims: Mother-to-child (MTC) hepatitis B virus (HBV) transmission has been mainly studied in Asia. The geographical origins of women and HBV genotypes differ in Europe. The aims were to determine the rate and risk factors of MTC HBV transmission from women with high HBV DNA loads in a maternity hospital in Paris, France.

Dynamics of cytomegalovirus populations harbouring mutations in genes UL54 and UL97 in a haematopoietic stem cell transplant recipient.

We characterised by pyrosequencing, the dynamics of cytomegalovirus populations harbouring mutations A594V in gene UL97 and A834P and Q578H in gene UL54 in a haematopoietic stem cell transplant recipient. Unexpected re-emergence of A594V and decrease of A834P under CMX001 were shown to depend on both the selection pressure exerted by the antiviral treatments and the immune response.

Stability and antiviral activity against human cytomegalovirus of artemisinin derivatives.

Objectives: Artesunate, a derivative of dihydroartemisinin, itself a product of artemisinin, inhibits the replication of cytomegalovirus in vitro. In vivo, artesunate undergoes rapid conversion into the active metabolite dihydroartemisinin. The in vitro stability of the compounds and the antiviral activity of dihydroartemisinin are of great concern for the interpretation of in vitro testing.

Maribavir use in practice for cytomegalovirus infection in French transplantation centers.

Maribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses.

Fully automated quantification of cytomegalovirus (CMV) in whole blood with the new sensitive Abbott RealTime CMV assay in the era of the CMV international standard.

Fully standardized reproducible and sensitive quantification assays for cytomegalovirus (CMV) are needed to better define thresholds for antiviral therapy initiation and interruption. We evaluated the newly released Abbott RealTime CMV assay for CMV quantification in whole blood (WB) that includes automated extraction and amplification (m2000 RealTime system). Sensitivity, accuracy, linearity, and intra- and interassay variability were validated in a WB matrix using Quality Control for Molecular Diagnostics (QCMD) panels and the WHO international standard (IS).

Eight flavonoids and their potential as inhibitors of human cytomegalovirus replication.

The drugs currently available for treatment of severe human cytomegalovirus (HCMV) infections suffer from many drawbacks, particularly toxicity, and potential teratogenicity contraindicating their use in target populations such as pregnant women. The emergence of drug-resistant strains is still a problem for disease management, particularly in immunosuppressed populations where antivirals are used for extended periods of time. The flavonoid family of drugs contains promising candidates as they have low toxicity and inhibit different targets to currently available antivirals.

[Large diversity of routine methods used for monitoring human cytomegalovirus infections in France].

Unlabelled: Monitoring cytomegalovirus circulating viral load is an important parameter of the follow-up in immunocompromised patients. It can be measured either by DNAemia or by pp65 antigenemia. The French national reference center for cytomegaloviruses organized an investigation of practice in 37 teacher hospital virology laboratories to assess the situation in France in 2010.

Hepatitis E virus infection in HIV-infected patients with elevated serum transaminases levels.

Increases in aminotransferases levels are frequently encountered in HIV-positive patients and often remain unexplained. The role in this setting and natural history of hepatitis E in HIV-infected patients are unknown. The aim of the study was to assess HEV infection in HIV-infected patients attending a Parisian hospital, with a current or previous cryptogenic hepatitis.

Antiviral activity of ganciclovir and artesunate towards human cytomegalovirus in astrocytoma cells.

Antimalarial drug artesunate inhibits cytomegalovirus (HCMV) replication in human fibroblasts. Astrocytes, the major cell type of the brain, support cytomegalovirus (HCMV) replication. The aim of the study was to assess the antiviral activity of artesunate in astrocytoma cell line U373MG in comparison with ganciclovir.

Drug-resistant cytomegalovirus in transplant recipients: a French cohort study.

Objectives: Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.

Description of liver disease in a cohort of HIV/HBV coinfected patients.

Background: Factors associated with advanced liver disease have been incompletely explored in HIV/HBV coinfected patients.

Objectives: To describe liver-related morbidity, mortality, and related risk factors, in HIV/HBV coinfected patients.

Study Design: We followed-up 107 consecutive HIV/HBV coinfected patients.

[Should patients infected with HIV be screened for occult hepatitis B?].

Unlabelled: Occult hepatitis B is defined as the presence of hepatitis B virus (HBV) DNA in the absence of detectable HBs antigen. The prevalence of occult hepatitis B among patients HIV-infected is uncertain, varying between 0% and 89%, and the clinical consequences of the coinfection are poorly known. The aim of this study was to evaluate the frequency of occult hepatitis B among HIV-infected patients and determine risk factors.

Rapid determination of antiviral drug susceptibility of human cytomegalovirus by real-time PCR.

A quantitative real-time PCR-based assay was developed for determination of cytomegalovirus (HCMV) susceptibility to antiviral drugs. After HCMV isolate-growth for 4 days, antiviral drug susceptibility was determined by measuring the reduction of intracellular HCMV DNA in the presence of increasing concentrations of either ganciclovir, or foscarnet or cidofovir. The 50% inhibitory concentration (IC(50)) was the drug concentration that reduced the number of HCMV genome copies by 50%.

Putative functional domains of human cytomegalovirus pUL56 involved in dimerization and benzimidazole D-ribonucleoside activity.

Background: Benzimidazole D-ribonucleosides inhibit DNA packaging during human cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56 and pUL89 (the large and small subunits of the HCMV terminase, respectively) their mechanism of action is not yet fully understood. We aimed here to better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives.

New functional domains of human cytomegalovirus pUL89 predicted by sequence analysis and three-dimensional modelling of the catalytic site DEXDc.

Introduction: Benzimidazole D-ribonucleosides inhibit DNA packaging during human cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56 and pUL89, the large and small subunits of the HCMV terminase respectively, their mechanism of action is not yet fully understood.

Methods And Results: To better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives, we studied the HCMV pUL89 protein by a genetic approach combined with primary structure analysis.