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Ellen Van Damme, Kim Thys, Marianne Tuefferd, Carl Van Hove, Jeroen Aerssens, Marnix Van Loock
Human cytomegalovirus (HCMV) is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs). This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages...
2016: PloS One
Sanne Duinkerken, Yvette van Kooyk, Juan J Garcia-Vallejo
Glioblastoma multiforme (GBM) is the most aggressive brain tumor and median survival time with current therapies is only 14.6 mo. Although multiple immunotherapeutic strategies are being explored, efficacy remains poor. In order to improve immunotherapy for GBM, we propose to combine currently used endogenous with human cytomegalovirus (HCMV) specific antigens expressed on cancer cells.
2016: Oncoimmunology
Lingfang Li, Yifan Li, Ziyu Dai, Meitong Liu, Bing Wang, Shuiping Liu, Lili Wang, Liyu Chen, Yurong Tan, Guojun Wu
BACKGROUND: The present study was designed to observe the infection of human cytomegalovirus (HCMV) to human vascular smooth muscle cells (VSMCs), and the effect of viral infection on lipid metabolism in VSMCs. METHODS: The cytopathic effects were observed by inverted microscopy and viral infection were examined by electron microscopy and RT-PCR. The lipid metabolism related gene profiling of VSMCs after HCMV infection was assayed by cDNA assay and the abnormal expression of genes were validated by quantitative RT-PCR...
October 17, 2016: Cellular Physiology and Biochemistry
Benedetta Pignoloni, Cinzia Fionda, Valentina Dell'Oste, Anna Luganini, Marco Cippitelli, Alessandra Zingoni, Santo Landolfo, Giorgio Gribaudo, Angela Santoni, Cristina Cerboni
Elimination of virus-infected cells by cytotoxic lymphocytes is triggered by activating receptors, among which NKG2D and DNAM-1/CD226 play an important role. Their ligands, that is, MHC class I-related chain (MIC) A/B and UL16-binding proteins (ULBP)1-6 (NKG2D ligand), Nectin-2/CD112, and poliovirus receptor (PVR)/CD155 (DNAM-1 ligand), are often induced on virus-infected cells, although some viruses, including human CMV (HCMV), can block their expression. In this study, we report that infection of different cell types with laboratory or low-passage HCMV strains upregulated MICA, ULBP3, and PVR, with NKG2D and DNAM-1 playing a role in NK cell-mediated lysis of infected cells...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Bingjun Bai, Xingxing Wang, Engeng Chen, Hongbo Zhu
Human cytomegalovirus infection (HCMV) has been recently considered as a factor for tumorigenesis. The current study used meta-analytical techniques to explore the prevalence of HCMV in tumor tissues and the relationship between human cytomegalovirus and colorectal cancer (CRC) risk. 11 studies detecting HCMV DNA in tumor tissues were included in meta-analysis. The prevalence rate and odds ratio (OR) were two main parameters. The overall prevalence of human cytomegalovirus DNA in tumor tissues were 27.5% (95% CI = 17...
October 8, 2016: Oncotarget
Elisa Gabanti, Francesca Bruno, Lucia Scaramuzzi, Filippo Mangione, Paola Zelini, Giuseppe Gerna, Daniele Lilleri
Human cytomegalovirus (HCMV) is still the most common viral infection in solid-organ transplant recipients (SOTR). Our study aimed to identify the predictive values of the T-cell response able to protect from HCMV disease, according to different assays. Viral DNA was determined by real-time PCR. The T-cell immune response to HCMV infection was investigated in SOTR according to the following assays and stimuli: cytokine flow cytometry (CFC) after peripheral blood mononuclear cell (PBMC) stimulation with autologous HCMV-infected dendritic cells (iDC) vs three ELISPOT assays using PBMCs stimulated with: i) HCMV-infected cell lysate (iCL); ii) a pool of 34 epitopic peptides (PP) from different HCMV proteins; iii) a commercial pp65 peptide pool (CPM)...
September 13, 2016: New Microbiologica
Xinhui Wang, Ming Hu, Feifei Xing, Mengyuan Wang, Bing Wang, Dongmeng Qian
Glioblastoma (GBM) are the most common and aggressive tumors of human brain. Recent studies showed that human cytomegalovirus (HCMV) can induce malignant transformation of tumor cells to maintain stemness. Transcription factor 5 (ATF5) is an anti-apoptotic protein that is highly expressed in malignant glioma. The aim of this study is to investigate the effect of HCMV infection on the stem cell makers of U251 cells. U251 cells were infected by AD169 HCMV strain (MOI = 1). The expression of stem cell makers (CD133, NES, Notch1) in infected U251 cells were compared with the expression in uninfected U251 cell to see the difference between them...
October 7, 2016: Journal of Medical Virology
G Michael Rebmann, Robert Grabski, Veronica Sanchez, William J Britt
: Human cytomegalovirus (HCMV) is the largest member of the Herpesviridae and represents a significant cause of disease. During virus replication, HCMV alters cellular functions to facilitate its replication, including significant reorganization of the secretory and endocytic pathways of the infected cell. A defining morphologic change of the infected cell is the formation of a membranous structure in the cytoplasm that is designated the virion assembly compartment (AC), which consists of virion structural proteins surrounded by cellular membranes...
October 4, 2016: MBio
Roberta Rizzo, Liliana Gabrielli, Daria Bortolotti, Valentina Gentili, Giulia Piccirilli, Angela Chiereghin, Claudia Pavia, Silvia Bolzani, Brunella Guerra, Giuliana Simonazzi, Francesca Cervi, Maria Grazia Capretti, Enrico Fainardi, Dario Di Luca, Maria Paola Landini, Tiziana Lazzarotto
Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection...
2016: Journal of Immunology Research
Corinne J Smith, Michael Quinn, Christopher M Snyder
Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8(+) T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8(+) T cell immunity...
2016: Frontiers in Immunology
D Topalis, S Gillemot, R Snoeck, G Andrei
Emergence of drug-resistance to all FDA-approved antiherpesvirus agents is an increasing concern in immunocompromised patients. Herpesvirus DNA polymerase (DNApol) is currently the target of nucleos(t)ide analogue-based therapy. Mutations in DNApol that confer resistance arose in immunocompromised patients infected with herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV), and to lesser extent in herpes simplex virus 2 (HSV-2), varicella zoster virus (VZV) and human herpesvirus 6 (HHV-6). In this review, we present distinct drug-resistant mutational profiles of herpesvirus DNApol...
September 29, 2016: Nucleic Acids Research
Michael Koldehoff, Stefan R Ross, Ulrich Dührsen, Dietrich W Beelen, Ahmet H Elmaagacli
A preventive effect of early human cytomegalovirus (HCMV) replication was evaluated in 136 non-Hodgkin lymphoma (NHL) patients with mature B-cell NHLs (n = 94), and mature T- and NK-cell NHLs (n = 42) after allogeneic stem cell transplantation (alloSCT). Most study-patients (85%) had received at least 2 cycles of chemotherapy and 60% had also received an autograft prior to alloSCT. First detection of CMV-replication by HCMV antigenemia/viremia was found at a median of day +33 after alloSCT. The cumulative incidence of relapse at 5 years after alloSCT was 38% (95% confidence interval [95%CI]: 26-49) in 82 patients without compared to 22% (95%CI: 8-37) in 54 patients with HCMV antigenemia/viremia (p = ...
August 10, 2016: Leukemia & Lymphoma
Mariella Della Chiesa, Silvia Pesce, Letizia Muccio, Simona Carlomagno, Simona Sivori, Alessandro Moretta, Emanuela Marcenaro
Human NK cells are distinguished into CD56(bright)CD16(-) cells and CD56(dim)CD16(+) cells. These two subsets are conventionally associated with differential functional outcomes and are heterogeneous with respect to the expression of KIR and CD94/NKG2 heterodimers that represent the two major types of HLA-class I-specific receptors. Recent studies indicated that immature CD56(bright) NK cells, homogeneously expressing the inhibitory CD94/NKG2A receptor, are precursors of CD56(dim) NK cells that, in turn, during their process of differentiation, lose expression of CD94/NKG2A and subsequentially acquire inhibitory KIRs and LIR-1...
2016: Frontiers in Immunology
Elisabeth A Pitt, Pranay Dogra, Ravi S Patel, Angela Williams, Jonathan S Wall, Tim E Sparer
Human cytomegalovirus (HCMV) infection in utero can lead to congenital sensory neural hearing loss and mental retardation. Reactivation or primary infection can increase the morbidity and mortality in immune suppressed transplant recipients and AIDS patients. The current standard of care for HCMV disease is nucleoside analogs, which can be nephrotoxic. In addition resistance to current treatments is becoming increasingly common. In an effort to develop novel CMV treatments, we tested the effectiveness of the D-form of a novel heparan sulfate binding peptide, p5RD, at reducing infection of ganciclovir (GCV) resistant HCMVs in vitro and MCMV in vivo...
September 25, 2016: Antiviral Research
Charlotte J Houldcroft, Josephine M Bryant, Daniel P Depledge, Ben K Margetts, Jacob Simmonds, Stephanos Nicolaou, Helena J Tutill, Rachel Williams, Austen J J Worth, Stephen D Marks, Paul Veys, Elizabeth Whittaker, Judith Breuer
Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks...
2016: Frontiers in Microbiology
Ya-Li Lv, Fei-Fei Han, Li-Li Gong, He Liu, Jun Ma, Wei-Yue Yu, Zi-Rui Wan, Yang-Jie Jia, Wen Zhang, Mingbiao Shi, Li-Hong Liu
BACKGROUND: Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease. Numbers studies were conducted to analyze the association between HCMV infection and risk of vascular disease, but no clear consensus had been reached. The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. METHODS: We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: (1) evaluating the association between HCMV infection and vascular disease; (2) case-control studies or nested case-control studies; (3) and supply the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively...
September 21, 2016: Virus Research
Jun Xiao, Xin Song, Jiang Deng, Liping Lv, Ping Ma, Bo Gao, Xipeng Zhou, Yanyu Zhang, Jinbo Xu
Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H2O2) stimulation, mediated by the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. However, it remains unknown whether host gene expression is involved in H2O2-upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H2O2 in a dose-dependent manner. Experiments with CyPA-specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H2O2-mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression...
September 2016: FEBS Open Bio
Pierre M Jean Beltran, Rommel A Mathias, Ileana M Cristea
The organelles within a eukaryotic host are manipulated by viruses to support successful virus replication and spread of infection, yet the global impact of viral infection on host organelles is poorly understood. Integrating microscopy, subcellular fractionation, mass spectrometry, and functional analyses, we conducted a cell-wide study of organelles in primary fibroblasts throughout the time course of human cytomegalovirus (HCMV) infection. We used label-free and isobaric-labeling proteomics to characterize nearly 4,000 host and 100 viral proteins, then classified their specific subcellular locations over time using machine learning...
September 14, 2016: Cell Systems
Takako Tabata, Matthew Petitt, June Fang-Hoover, Martin Zydek, Lenore Pereira
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects, including microcephaly, neurological deficits, hearing impairment, and vision loss. We previously reported that epithelial cells in amniotic membranes of placentas from newborns with intrauterine growth restriction and underlying congenital HCMV infection contain viral proteins in cytoplasmic vesicles. Herein, we immunostained amniotic membranes from 51 placentas from symptomatic and asymptomatic congenital infection with HCMV DNA in amniotic fluid and/or newborn saliva, intrauterine growth restriction, preterm deliveries, and controls...
September 13, 2016: American Journal of Pathology
Eleni Panagioti, Anke Redeker, Suzanne van Duikeren, Kees Lmc Franken, Jan Wouter Drijfhout, Sjoerd H van der Burg, Ramon Arens
There is an ultimate need for efficacious vaccines against human cytomegalovirus (HCMV), which causes severe morbidity and mortality among neonates and immunocompromised individuals. In this study we explored synthetic long peptide (SLP) vaccination as a platform modality to protect against mouse CMV (MCMV) infection in preclinical mouse models. In both C57BL/6 and BALB/c mouse strains, prime-booster vaccination with SLPs containing MHC class I restricted epitopes of MCMV resulted in the induction of strong and polyfunctional (i...
September 2016: PLoS Pathogens
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