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https://www.readbyqxmd.com/read/28428537/human-cytomegalovirus-induces-cellular-and-humoral-virus-specific-immune-responses-in-humanized-blt-mice
#1
Lindsey B Crawford, Rebecca Tempel, Daniel N Streblow, Craig Kreklywich, Patricia Smith, Louis J Picker, Jay A Nelson, Patrizia Caposio
The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424684/modulation-of-human-leukocyte-antigen-c-by-human-cytomegalovirus-stimulates-kir2ds1-recognition-by-natural-killer-cells
#2
Kattria van der Ploeg, Chiwen Chang, Martin A Ivarsson, Ashley Moffett, Mark R Wills, John Trowsdale
The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420741/new-mechanism-by-which-human-cytomegalovirus-micrornas-negate-the-proinflammatory-response-to-infection
#3
Andrew D Yurochko
Viruses have evolved many novel mechanisms to promote infection and to mitigate the host cell response to that infection. In the article by M. H. Hancock et al. (mBio 8:e00109-17, 2017, https://doi.org/10.1128/mBio.00109-17), the authors describe a new mechanism by which human cytomegalovirus (HCMV) microRNAs (miRNAs; miR-US5-1 and miR-UL112-3p) negate the proinflammatory response to infection. The authors document that these two viral miRNAs downregulate the NF-κB response through direct targeting of the IKKα and IKKβ mRNAs, which in turn, through diminished IκB kinases (IKKs), block production of proinflammatory cytokines (interleukin-6 [IL-6], CCL5, and tumor necrosis factor alpha [TNF-α])...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28415934/early-abnormal-liver-enzyme-levels-may-increase-the-prevalence-of-human-cytomegalovirus-antigenaemia-after-hematopoietic-stem-cell-transplantation
#4
Baning Ye, Hong Zhao
Objective Human cytomegalovirus (HCMV) infection is common after bone marrow transplantation (BMT), and it increases morbidity and mortality for transplant recipients. HCMV infection may cause hepatitis and elevate the liver enzymes aspartate transferase (AST) and alanine transferase (ALT). This study aimed to analyse the associations between liver enzyme levels and infection with HCMV antigenaemia after BMT. Methods Data from 30 patients after BMT were collected at different time points (0.5, 1.0, 1.5, 2.0, 2...
April 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28415933/incidence-risk-factors-and-the-effect-of-polyomavirus-infection-in-hematopoietic-stem-cell-transplant-recipients
#5
Jianhua Hu, Siying Li, Meifang Yang, Lichen Xu, Xuan Zhang, Hong Zhao, Huihui Dong, Yaping Huang, Jun Fan, Lanjuan Li
Objective The effect of polyomavirus infection in HSCT recipients is poorly understood. Methods We evaluated 38 HSCT recipients. Polyomavirus was detected by nested qualitative polymerase chain reaction (PCR) assays of urine. The risk factors for BK virus and JC virus were analysed. The kidney and liver functions of infected and uninfected patients were compared. Results BK virus, JC virus, and simian virus 40 were detected in 21%, 42%, and 0% of HSCT recipients respectively. HCMV infection was found to be an independent risk factor for JC virus infection (odds ratio (OR): 8...
April 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28407276/synthesis-characterization-and-biological-evaluation-of-some-novel-quinoxaline-derivatives-as-antiviral-agents
#6
Heba S A El-Zahabi
Ethyl (6,7-dimethyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate and ethyl (6-methyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate (1a,b), 3-methylquinoxalin-2(1H)-one (4) and 1,4-dihydroquinoxaline-2,3-dione (11) were the starting precursors for nine novel quinoxaline compounds, 3a, 6, 10, 13, 15, 16, 17, 18, and 20, via adopting different nucleophilic reactions. The synthesized compounds were tested for their antiviral activity against HCV, HBV, HSV-1, and HCMV. Concomitantly, their safety profile was investigated as well as their selectivity against the viral strains...
April 13, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28407004/epigenetically-repressing-human-cytomegalovirus-lytic-infection-and-reactivation-from-latency-in-thp-1-model-by-targeting-h3k9-and-h3k27-histone-demethylases
#7
Xin Gan, Haifeng Wang, Yanyan Yu, Wei Yi, Shanshan Zhu, En Li, Yu Liang
Human Cytomegalovirus (hCMV) infects a broad range of the population and establishes life-long latency in the infected individuals. Periodically the latently infected virus can reactivate and becomes a significant cause of morbidity and mortality in immunocompromised individuals. In latent infection, the viral genome is suppressed in a heterochromatic state and viral gene transcription is silenced. Upon reactivation, the repressive chromatin is remodeled to an active form, allowing viral lytic gene transcription, initiated by the expression of viral Immediate Early (IE) genes...
2017: PloS One
https://www.readbyqxmd.com/read/28406138/inhibition-of-endocytic-pathways-impacts-cytomegalovirus-maturation
#8
Madeline A Archer, Teal M Brechtel, Leslie E Davis, Rinkuben C Parmar, Mohammad H Hasan, Ritesh Tandon
Endocytic processes are critical for cellular entry of several viruses; however, the role of endocytosis in cellular trafficking of viruses beyond virus entry is only partially understood. Here, we utilized two laboratory strains (AD169 and Towne) of human cytomegalovirus (HCMV), which are known to use cell membrane fusion rather than endocytosis to enter fibroblasts, in order to study a post-entry role of endocytosis in HCMV life cycle. Upon pharmacological inhibition of dynamin-2 or clathrin terminal domain (TD) ligand association, these strains entered the cells successfully based on the expression of immediate early viral protein...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28403220/a-derivative-of-platelet-derived-growth-factor-receptor-alpha-binds-to-the-trimer-of-human-cytomegalovirus-and-inhibits-entry-into-fibroblasts-and-endothelial-cells
#9
Cora Stegmann, Daniel Hochdorfer, Diana Lieber, Narmadha Subramanian, Dagmar Stöhr, Kerstin Laib Sampaio, Christian Sinzger
Human cytomegalovirus (HCMV) is a widely distributed herpesvirus that causes significant morbidity in immunocompromised hosts. Inhibitors of viral DNA replication are available, but adverse effects limit their use. Alternative antiviral strategies may include inhibition of entry. We show that soluble derivatives of the platelet-derived growth factor receptor alpha (PDGFR-alpha), a putative receptor of HCMV, can inhibit HCMV infection of various cell types. A PDGFR-alpha-Fc fusion protein binds to and neutralizes cell-free virus particles at an EC50 of 10-30 ng/ml...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28403202/human-cytomegalovirus-glycoprotein-complex-gh-gl-go-uses-pdgfr-%C3%AE-as-a-key-for-entry
#10
Yiquan Wu, Adrian Prager, Simone Boos, Moritz Resch, Ilija Brizic, Michael Mach, Sabrina Wildner, Laura Scrivano, Barbara Adler
Herpesvirus gH/gL envelope glycoprotein complexes are key players in virus entry as ligands for host cell receptors and by promoting fusion of viral envelopes with cellular membranes. Human cytomegalovirus (HCMV) has two alternative gH/gL complexes, gH/gL/gO and gH/gL/UL128,130,131A which both shape the HCMV tropism. By studying binding of HCMV particles to fibroblasts, we could for the first time show that virion gH/gL/gO binds to platelet-derived growth factor-α (PDGFR-α) on the surface of fibroblasts and that gH/gL/gO either directly or indirectly recruits gB to this complex...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28402975/frequent-pul27-variations-in-hiv-infected-patients
#11
Azam Mirarab, Alireza Mohebbi, Abdolvahab Moradi, Naeme Javid, Mohammad Ali Vakili, Alijan Tabarraei
OBJECTIVE: Drug-resistant isolates of human cytomegalovirus (HCMV) have led to the development of new anti-HCMV drugs. Maribavir (MBV) is a novel inhibitor of the HCMV viral kinase. Resistance to MBV is mapped to gene UL27, a viral nuclear protein. In this study, we investigated UL27 polymorphisms in MBV-naive HIV-positive and HCMV congenitally infected clinical samples. METHODS: DNA was extracted from 20 CMV-positive HIV (9/20) and congenitally infected (11/20) patients and used for UL27 polymerase chain reaction amplification...
April 13, 2017: Intervirology
https://www.readbyqxmd.com/read/28400599/lps-promotes-a-monocyte-phenotype-permissive-for-human-cytomegalovirus-immediate-early-gene-expression-upon-infection-but-not-reactivation-from-latency
#12
V G Kew, M R Wills, M B Reeves
Human cytomegalovirus (HCMV) infection of myeloid cells is closely linked with the differentiation status of the cell. Haematopoietic progenitors and CD14+ monocytes are usually non-permissive for lytic gene expression which can lead to the establishment of latent infections. In contrast, differentiation to macrophage or dendritic cell (DC) phenotypes promotes viral reactivation or renders them permissive for lytic infection. The observation that high doses of Lipopolysaccharide (LPS) drove rapid monocyte differentiation in mice led us to investigate the response of human monocytes to HCMV following LPS stimulation in vitro...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400201/inhibitors-of-dual-specificity-tyrosine-phosphorylation-regulated-kinases-dyrk-exert-a-strong-anti-herpesviral-activity
#13
Corina Hutterer, Jens Milbradt, Stuart Hamilton, Mirko Zaja, Johann Leban, Christophe Henry, Daniel Vitt, Mirjam Steingruber, Eric Sonntag, Isabel Zeitträger, Hanife Bahsi, Thomas Stamminger, William Rawlinson, Stefan Strobl, Manfred Marschall
Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of (val)ganciclovir therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy of antiviral treatment is based on the exploitation of cell-directed signaling, e. g. pathways with a known relevance for carcinogenesis and tumor drug development. Here we describe a principle for putative antiviral drugs based on targeting dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs)...
April 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28398495/a-histological-study-of-fulminant-type-1-diabetes-mellitus-related-to-human-cytomegalovirus-reactivation
#14
Sho Yoneda, Akihisa Imagawa, Kenji Fukui, Sae Uno, Junji Kozawa, Makoto Sakai, Toshiki Yumioka, Hiromi Iwahashi, Iichiro Shimomura
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: We determined the localization of viruses of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells by immunohistochemistry of pancreas from an autopsy fulminant T1DM patient with DIHS or seven subjects with normal glucose tolerance who underwent pancreatectomy...
April 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28392788/the-transcription-factor-hobit-identifies-human-cytotoxic-cd4-t-cells
#15
Anna E Oja, Felipe A Vieira Braga, Ester B M Remmerswaal, Natasja A M Kragten, Kirsten M L Hertoghs, Jianmin Zuo, Paul A Moss, René A W van Lier, Klaas P J M van Gisbergen, Pleun Hombrink
The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4(+) T cells that conforms to the phenotype of cytotoxic CD8(+) T cells has received increased recognition. These cytotoxic CD4(+) T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28391502/genomic-analysis-of-chimeric-human-cytomegalovirus-vaccine-candidates-derived-from-strains-towne-and-toledo
#16
Nicolás M Suárez, Betty Lau, George M Kemble, Ronzo Lee, Edward S Mocarski, Gavin W G Wilkinson, Stuart P Adler, Michael A McVoy, Andrew J Davison
Human cytomegalovirus (HCMV) is an important opportunistic pathogen in immunocompromised patients and a major cause of congenital birth defects when acquired in utero. In the 1990s, four chimeric viruses were constructed by replacing genome segments of the high passage Towne strain with segments of the low passage Toledo strain, with the goal of obtaining live attenuated vaccine candidates that remained safe but were more immunogenic than the overly attenuated Towne vaccine. The chimeras were found to be safe when administered to HCMV-seronegative human volunteers, but to differ significantly in their ability to induce seroconversion...
April 8, 2017: Virus Genes
https://www.readbyqxmd.com/read/28390939/guanine-%C3%AE-carboxy-nucleoside-phosphonate-g-%C3%AE-cnp-shows-a-different-inhibitory-kinetic-profile-against-the-dna-polymerases-of-human-immunodeficiency-virus-hiv-and-herpes-viruses
#17
Jan Balzarini, Michael Menni, Kalyan Das, Lizette van Berckelaer, Alan Ford, Nuala M Maguire, Sandra Liekens, Paul E Boehmer, Eddy Arnold, Matthias Götte, Anita R Maguire
α-Carboxy nucleoside phosphonates (α-CNPs) are modified nucleotides that represent a novel class of nucleotide-competing reverse transcriptase (RT) inhibitors (NcRTIs). They were designed to act directly against HIV-1 RT without the need for prior activation (phosphorylation). In this respect, they differ from the nucleoside or nucleotide RTIs [N(t)RTIs] that require conversion to their triphosphate forms before being inhibitory to HIV-1 RT. The guanine derivative (G-α-CNP) has now been synthesized and investigated for the first time...
April 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28383788/replication-stress-dna-damage-signalling-and-cytomegalovirus-infection-in-human-medulloblastomas
#18
Jiri Bartek, Olesja Fornara, Joanna Maria Merchut-Maya, Apolinar Maya-Mendoza, Afshar Rahbar, Giuseppe Stragliotto, Helle Broholm, Mikael Svensson, Astrid Sehested, Cecilia Söderberg Naucler, Jiri Bartek, Jirina Bartkova
Medulloblastomas are the most common, and often fatal, paediatric brain tumours that feature high genomic instability, frequent infection by human cytomegalovirus (HCMV) and resistance to radiation and chemotherapy. The causes of the pronounced chromosomal instability and its potential links with HCMV infection and/or resistance to genotoxic therapies remain largely unknown. To address these issues, here we have combined immunohistochemical analysis of a series of 25 paediatric medulloblastomas, complemented by medulloblastoma cell culture models including experimental HCMV infection...
April 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28383105/enhancement-of-cytokine-driven-nk-cell-ifn-%C3%AE-production-after-vaccination-of-hcmv-infected-africans
#19
Alansana Darboe, Ebrima Danso, Ed Clarke, Ama Umesi, Ebrima Touray, Rita Wegmuller, Sophie E Moore, Eleanor M Riley, Martin R Goodier
Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28368496/characterization-of-human-cytomegalovirus-genome-diversity-in-immunocompromised-hosts-by-whole-genomic-sequencing-directly-from-clinical-specimens
#20
E Hage, G S Wilkie, S Linnenweber-Held, A Dhingra, N M Suárez, J J Schmidt, P Kay-Fedorov, E Mischak-Weissinger, A Heim, A Schwarz, T F Schulz, A J Davison, T Ganzenmueller
Background: Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals. Methods: NGS was performed on target-enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast-milk, respiratory samples, biopsies and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients and congenitally infected children)...
March 27, 2017: Journal of Infectious Diseases
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