Hcmv

NK cells play a decisive role in controlling hCMV infection by combining innate and adaptive-like immune reactions. The hCMV-derived VMAPRTLFL (LFL) peptide is a potent activator of NKG2C+ NK cells. Proposed here is an autologous system of LFL stimulation without T lymphocytes and exogenous cytokines that allows us to evaluate NK-cell hCMV-specific responses in more native settings. In this model, we evaluated LFL-induced IFNγ production, focusing on signaling pathways and the degranulation and proliferation of NK cells orchestrated by microenvironment cytokine production and analyzed the transcriptome of expanded NK cells...

One major risk for recipients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCTs) is infection with the human cytomegalovirus (HCMV). For HCMV treatment, it is especially crucial to be able to differentiate between recipients who are at high risk of reactivation and those who are not. In this study, HCMV-DNA was collected from 60 HLA-A*02 allo-HSCT recipients before and after transplantation. After transplantation, the release of interferon (IFN)-γ by T cells specific to HCMV was assessed using the enzyme-linked immunospot assay (ELISPOT)...

mRNA-1647 is an investigational mRNA-based vaccine against cytomegalovirus (CMV) that contains sequences encoding the CMV proteins glycoprotein B and pentamer. Humoral and cellular immune responses were evaluated in blood samples collected from healthy CMV-seropositive and CMV-seronegative adults who participated in a phase 1 trial of a three-dose series of mRNA-1647 (NCT03382405). Neutralizing antibody (nAb) titers against fibroblast and epithelial cell infection in sera from CMV-seronegative mRNA-1647 recipients were higher than those in sera from control CMV-seropositive samples and remained elevated up to 12 months after dose 3...

Human cytomegalovirus infection usually proceeds asymptomatically in immunocompetent patients. In symptomatic forms, mononucleosis syndrome is the most common manifestation. However, atypical cases of cytomegalovirus infections in immunocompetent subjects are reported in the literature. Here, we describe a case of cytomegalovirus-related mononucleosis syndrome that presented with an atypical erythema multiforme-like skin rash and high fever. Very few cases have been described in the literature previously. In our case, the diagnosis was supported by specific serology, and human cytomegalovirus DNA was detected in the blood sample...

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups...

Interferon-gamma (IFNγ) ELISpot and FluoroSpot are widely used assays to detect functional cell responses in immunotherapy clinical studies. Recognized for their importance in vaccine development studies to quantitate immune responses, these assays have more recently risen to the forefront in cell and gene therapy as well as cancer immunotherapy fields where responses against cancer neoantigens are not easily detectable above assay background. Here, we test a new class of fetal bovine serum (FBS), CultraPure FBS, in ex vivo ELISpot and FluoroSpot assays and cultured FluoroSpot assays following in vitro expansion...

Latent human cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals. Although T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in hCMV immunity is lacking. Here, in an unbiased manner, we characterized over 8000 hCMV-reactive peripheral memory T cells isolated from seropositive human donors, at a single-cell resolution by analysing their single-cell transcriptomes paired with the T cell antigen receptor (TCR) repertoires...

Human cytomegalovirus (HCMV) infection of monocytes is essential for viral dissemination and persistence. We previously identified that HCMV entry/internalization and subsequent productive infection of this clinically relevant cell type is distinct when compared to other infected cells. We showed that internalization and productive infection required activation of epidermal growth factor receptor (EGFR) and integrin/c-Src, via binding of viral glycoprotein B to EGFR, and the pentamer complex to β1/β3 integrins...

Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC)...

The herpesviral nuclear egress represents an essential step of viral replication efficiency in host cells, as it defines the nucleocytoplasmic release of viral capsids. Due to the size limitation of the nuclear pores, viral nuclear capsids are unable to traverse the nuclear envelope without a destabilization of this natural host-specific barrier. To this end, herpesviruses evolved the regulatory nuclear egress complex (NEC), composed of a heterodimer unit of two conserved viral NEC proteins (core NEC) and a large-size extension of this complex including various viral and cellular NEC-associated proteins (multicomponent NEC)...

The STimulator of INterferon Genes (STING) constitutes a major DNA-sensing pathway that restricts HSV-1 infection in different models by activating type I interferon and pro-inflammatory responses. To counteract STING, HSV-1 has evolved numerous strategies including mechanisms to interfere with its oligomerization, post-translational modifications, and downstream signaling. Previously, we demonstrated that STING is packaged in extracellular vesicles (EVs) produced from HSV-1-infected cells. These EVs activated antiviral responses in uninfected recipient cells and suppressed a subsequent HSV-1 infection in a STING-dependent manner...

Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro , but their role in infection and pathogenesis is unknown. To examine the in vivo function of vFcγRs in animal hosts closely related to humans, we identified and characterized vFcγRs encoded by rhesus CMV (RhCMV). We demonstrate that Rh05, Rh152/151 and Rh173 represent the complete set of RhCMV vFcγRs, each displaying functional similarities to their respective HCMV orthologs with respect to antagonizing host FcγR activation in vitro ...

G protein coupled receptors (GPCRs) are seven-transmembrane domain proteins that modulate cellular processes in response to external stimuli. These receptors represent the largest family of membrane proteins, and in mammals, their signaling regulates important physiological functions, such as vision, taste, and olfaction. Many organisms, including yeast, slime molds, and viruses encode GPCRs. Cytomegaloviruses (CMVs) are large, betaherpesviruses, that encode viral GPCRs (vGPCRs). Human CMV (HCMV) encodes four vGPCRs, including UL33, UL78, US27, and US28...

Human cytomegalovirus (HCMV) is an opportunistic pathogen causing severe diseases in immunosuppressed individuals. To replicate its double-stranded DNA genome, HCMV induces profound changes in cellular homeostasis that may resemble senescence. However, it remains to be determined whether HCMV-induced senescence contributes to organ-specific pathogenesis. Here, we show a direct cytopathic effect of HCMV on primary renal proximal tubular epithelial cells (RPTECs), a natural setting of HCMV disease. We find that RPTECs are fully permissive for HCMV replication, which endows them with an inflammatory gene signature resembling the senescence-associated secretory phenotype (SASP), as confirmed by the presence of the recently established SenMayo gene set, which is not observed in retina-derived epithelial (ARPE-19) cells...

UNLABELLED: Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs), syncytiotrophoblasts (STBs), and organoids, and this study assessed the utility of TSCs as a model of HCMV infection in the first-trimester placenta...

UNLABELLED: Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. Viruses correlated with congenital hearing loss include human cytomegalovirus (HCMV) and Zika virus (ZIKV), which causes congenital Zika syndrome. The mechanisms by which HCMV and ZIKV infections cause hearing loss are poorly understood. It is challenging to study human inner ear cells because they are encased in bone and also scarce as autopsy samples. Recent advances in culturing human stem cell-derived otic progenitor cells (OPCs) have allowed us herein to describe successful in vitro infection of OPCs with HCMV and ZIKV, and also to propose potential mechanisms by which each viral infection could affect hearing...

BACKGROUND: Human Cytomegalovirus (HCMV) is the most frequent congenital infection worldwide causing important sequelae. However, no vaccine or antiviral treatments are currently available, thus interventions are restricted to behavioral measures. The aim of this systematic review was to assess evidence from available intervention studies using hygiene-based measures to prevent HCMV infection during pregnancy. METHODS: Studies published from 1972 to 2023 were searched in Medline, PsycInfo, and Clinical Trials (PROSPERO, CRD42022344840) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines...

The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to "TORCH" infections (Toxoplasma gondii, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications...

Human cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them initiate viral gene expression. Increased viral gene expression is associated with activation of the stimulator of interferon genes (STING) that usually induces anti-viral interferon responses, and with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes...

Human cytomegalovirus (HCMV) is a prevalent pathogen that establishes life-long latent infection in hematopoietic cells. While this infection is usually asymptomatic, immune dysregulation leads to viral reactivation, which can cause significant morbidity and mortality. However, the mechanisms underpinning reactivation remain incompletely understood. The HCMV major immediate early promoter (MIEP)/enhancer is a key factor in this process, as its transactivation from a repressed to active state helps drive viral gene transcription necessary for reactivation from latency...