Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial.

Background: Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase.

Methods: In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case.

Towards a Prophylactic Vaccine for the Prevention of HCMV Infection.

Human cytomegalovirus (HCMV) or human herpesvirus 5, is a ubiquitous human herpesvirus, which can cause severe disease in immunocompromised patients (AIDS patients and solid organ transplant or hematopoietic stem cell transplant recipients) [...

New Insights into Human Cytomegalovirus pUL52 Structure.

Human cytomegalovirus (HCMV) can cause serious diseases in immunocompromised patients. Current antiviral inhibitors all target the viral DNA polymerase. They have adverse effects, and prolonged treatment can select for drug resistance mutations.

Post-herpetic encephalitis cerebral abscess: Viral reactivation or latency site within central nervous system?

Herpetic encephalitis results from central nervous system invasion by herpes simplex virus. We report the case of a man who developed a cerebral abscess fifteen months after initial Herpetic encephalitis. Retrospectively, antiviral should not have been associated with antibiotics during abscess episode, as transcriptomic analysis reported no viral reactivation.

Comprehensive Epstein-Barr Virus Transcriptome by RNA-Sequencing in Angioimmunoblastic T Cell Lymphoma (AITL) and Other Lymphomas.

The Epstein-Barr virus (EBV) is associated with angioimmunoblastic T cell lymphoma (AITL) in more than 80% of cases. Few studies have focused on this association and it is not clear now what role the virus plays in this pathology. We used next-generation sequencing (NGS) to study EBV transcriptome in 14 AITLs compared to 21 other lymphoma samples and 11 cell lines including 4 lymphoblastoid cell lines (LCLs).

Evaluation of Humoral Immunity to SARS-CoV-2: Diagnostic Value of a New Multiplex Addressable Laser Bead Immunoassay.

Despite efforts to develop anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody (Ab) immunoassays, reliable serological methods are still needed. We developed a multiplex addressable laser bead immunoassay (ALBIA) to detect and quantify anti-Spike S1 and nucleocapsid N Abs. Recombinant S1 and N proteins were bound to fluorescent beads (ALBIA-IgG-S1/N).

Cytomegalovirus (CMV) Shedding in French Day-Care Centers: A Nationwide Study of Epidemiology, Risk Factors, Centers' Practices, and Parents' Awareness of CMV.

Background: Congenital cytomegalovirus (CMV) remains an important healthcare burden, resulting from primary or secondary infection in pregnant women. Exposure to young children's saliva is a major risk factor, as prevalence of CMV shedding can reach 34%.

Methods: This cross-sectional, multicenter, nationwide study was conducted in randomly selected day care centers (DCCs), and complemented with a survey among parents and DCCs.

Letermovir for Secondary Prophylaxis of Cytomegalovirus Infection and Disease after Allogeneic Hematopoietic Cell Transplantation: Results from the French Compassionate Program.

Letermovir potently inhibits the cytomegalovirus (CMV)-terminase complex. Letermovir primary prophylaxis given for the first 3 months after allogeneic hematopoietic cell transplantation (HCT) has been shown to reduce clinically significant CMV infection and is well tolerated. Until now, only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis (SP) of CMV infection or diseases after HCT.

Diagnostic challenges of central nervous system infection: extensive multiplex panels versus stepwise guided approach.

Background: Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach.

Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication.

The human cytomegalovirus (HCMV) terminase complex is part of DNA-packaging machinery that delivers a unit-length genome into a procapsid. Sequence comparison of herpesvirus homologs allowed us to identify a potential LATLNDIERFL and zinc finger pattern in N-terminal part of pUL56. Recombinant viruses were generated with specific serine or alanine substitutions in these putative patterns.

Input of recombinant phenotyping for the characterization of a novel acyclovir-resistance mutation identified in a patient with recurrent herpetic keratitis.

We report here a case of an immunocompetent patient suffering from recurrent epithelial herpetic keratitis associated with the emergence of antiviral resistance. Indeed, the not previously described amino acid change L340R within herpes simplex virus thymidine kinase, was shown to confer acyclovir-resistance by recombinant phenotyping using bacmid technology.

Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis.

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.

Added value of ultra-deep sequencing (UDS) approach for detection of genotypic antiviral resistance of herpes simplex virus (HSV).

Classically, Sanger sequencing is considered the gold standard for detection of HSV drug resistance mutations (DRMs). As a complementary method, ultra-deep sequencing (UDS) has an improved ability to detect minor variants and mixed populations. The aim of this work was to apply UDS performed on MiSeq Illumina platform to the detection of HSV DRMs and to the evaluation of the subpopulation diversity in clinical samples in comparison with Sanger sequencing.

Implementing Universal Varicella Vaccination in Europe: The Path Forward.

Varicella is a common vaccine-preventable disease that usually presents as a mild disorder but can lead to severe complications. Before the implementation of universal varicella vaccination (UVV) in some European countries, the burden of varicella disease was broadly similar across the region. Despite this, countries adopted heterogeneous varicella vaccination strategies.

Identification of Amino Acids Essential for Viral Replication in the HCMV Helicase-Primase Complex.

Promising new inhibitors that target the viral helicase-primase complex have been reported to block replication of herpes simplex and varicella-zoster viruses, but they have no activity against human cytomegalovirus (HCMV), another herpesvirus. The HCMV helicase-primase complex (pUL105-pUL102-pUL70) is essential for viral DNA replication and could thus be a relevant antiviral target. The roles of the individual subunits composing this complex remain to be defined.

Development of a standardized real time PCR for Torque teno viruses (TTV) viral load detection and quantification: A new tool for immune monitoring.

Background: Torque teno viruses (TTV) are small DNA viruses whose replication is closely linked to immune status. A growing number of publications underlined the potential of TTV viral load as an indicator of immunosuppression.

Objectives: To demonstrate the analytical performance of the first standardized RUO (Research Use Only) assay to detect and quantify human TTV DNA in whole blood and plasma.

The human cytomegalovirus terminase complex as an antiviral target: a close-up view.

Human cytomegalovirus (HCMV) is responsible for life-threatening infections in immunocompromised individuals and can cause serious congenital malformations. Available antivirals target the viral polymerase but are subject to cross-resistance and toxicity. New antivirals targeting other replication steps and inducing fewer adverse effects are therefore needed.