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https://www.readbyqxmd.com/read/28741727/placental-pericytes-and-cytomegalovirus-infectivity-implications-for-hcmv-placental-pathology-and-congenital-disease
#1
David M Aronoff, Hernan Correa, Lisa M Rogers, Ravit Arav-Boger, Donald J Alcendor
PROBLEM: Placental pericytes are essential for placental microvascular function, stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis incorporating placental pericytes are unknown. METHOD OF STUDY: HCMV-infected placental tissue was stained by dual-labeled immunohistochemistry. Primary placental pericytes, cytotrophoblasts, and villous fibroblasts were exposed to HCMV; and infectivity was analyzed by microscopy and immunofluorescence...
July 25, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28718378/microrna-613-is-downregulated-in-hcmv-positive-glioblastoma-and-inhibits-tumour-progression-by-targeting-arginase-2
#2
Yan Wang, Peng Zhao, Dongmeng Qian, Ming Hu, Li Zhang, Hailei Shi, Bin Wang
Glioblastoma is the most common and malignant tumour that occurs primarily in nervous system and has a high morbidity. Research on glioblastoma has recently focused on human cytomegalovirus, belonging to the beta subfamily of Herpesviridae that plays crucial roles in cancer development and progression. This study aimed to investigate the role of human cytomegalovirus-associated microRNA-613 in glioblastoma. In this study, we demonstrate that microRNA-613 expression was frequently reduced in human cytomegalovirus-positive glioblastoma specimens/cells compared with human cytomegalovirus-negative glioblastoma tissue/cells, and a significant correlation was observed between the reduction in microRNA-613 expression and the presence of unfavourable variables, including tumour size (p = 0...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28704950/structure-activity-relationships-of-acyclic-selenopurine-nucleosides-as-antiviral-agents
#3
Pramod K Sahu, Tamima Umme, Jinha Yu, Gyudong Kim, Shuhao Qu, Siddhi D Naik, Lak Shin Jeong
A series of acyclic selenopurine nucleosides 3a-f and 4a-g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited the most potent anti-herpes simplex virus (HSV)-1 (EC50 = 1.47 µM) and HSV-2 (EC50 = 6.34 µM) activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e-g exhibited significant anti-human cytomegalovirus (HCMV) activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d)...
July 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28695489/lack-of-human-cytomegalovirus-expression-in-single-cells-from-glioblastoma-tumors-and-cell-lines
#4
Travis S Johnson, Zachary B Abrams, Xiaokui Mo, Yan Zhang, Kun Huang
The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) is an ongoing debate with extensive evidence supporting or refuting its existence through molecular assays, pre-clinical studies, and clinical trials. We focus primarily on the crux of the debate, detection of HCMV in GBM samples using molecular assays. We propose that these differences in detection could be affected by cellular heterogeneity. To take this into account, we align the single-cell RNA sequencing (scRNA-seq) reads from five GBM tumors and two cell lines to HCMV and analyze the alignments for evidence of (i) complete viral transcripts and (ii) low-abundance viral reads...
July 10, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28694811/latent-cytomegalovirus-cmv-infection-does-not-detrimentally-alter-t-cell-responses-in-the-healthy-old-but-increased-latent-cmv-carriage-is-related-to-expanded-cmv-specific-t-cells
#5
Sarah E Jackson, George X Sedikides, Georgina Okecha, Emma L Poole, John H Sinclair, Mark R Wills
Human cytomegalovirus (HCMV) primary infection and periodic reactivation of latent virus is generally well controlled by T-cell responses in healthy people. In older donors, overt HCMV disease is not generally seen despite the association of HCMV infection with increased risk of mortality. However, increases in HCMV DNA in urine of older people suggest that, although the immune response retains functionality, immunomodulation of the immune response due to lifelong viral carriage may alter its efficacy. Viral transcription is limited during latency to a handful of viral genes and there is both an IFNγ and cellular IL-10 CD4(+) T-cell response to HCMV latency-associated proteins...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28682067/expanding-the-antiviral-spectrum-of-3-fluoro-2-phosphonomethoxy-propyl-acyclic-nucleoside-phosphonates-diamyl-aspartate-amidate-prodrugs
#6
Min Luo, Elisabetta Groaz, Graciela Andrei, Robert Snoeck, Raj Kalkeri, Roger G Ptak, Tracy Hartman, Robert W Buckheit, Dominique Schols, Steven De Jonghe, Piet Herdewijn
Acyclic nucleosides containing a 3-fluoro-2-(phosphonomethoxy)propyl (FPMP) side chain are known to be moderately potent antihuman immunodeficiency virus (HIV) agents, while being completely devoid of antiviral activity against a wide range of DNA viruses. The derivatization of the phosphonic acid functionality of FPMPs with a diamyl aspartate phenoxyamidate group led to a novel generation of compounds that not only demonstrate drastically improved antiretroviral potency but also are characterized by an expanded spectrum of activity that also covers hepatitis B and herpes viruses...
July 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28681110/recent-advances-in-cmv-tropism-latency-and-diagnosis-during-aging
#7
Sean X Leng, Jeremy Kamil, John G Purdy, Niels A Lemmermann, Matthias J Reddehase, Felicia D Goodrum
Human cytomegalovirus (CMV) is one of the largest viruses known to cause human diseases. Chronic CMV infection, as defined by anti-CMV IgG serology, increases with age and is highly prevalent in older adults. It has complex biology with significant immunologic and health consequences. This article aims to summarize research findings presented at the 6th International Workshop on CMV and Immunosenescence that relate to advances in the areas of CMV tropism, latency, CMV manipulation of cell metabolism, and T cell memory inflation, as well as novel diagnostic evaluation and translational research of chronic CMV infection in older adults...
June 2017: GeroScience
https://www.readbyqxmd.com/read/28679960/preexisting-antibodies-can-protect-against-congenital-cytomegalovirus-infection-in-monkeys
#8
Cody S Nelson, Diana Vera Cruz, Dollnovan Tran, Kristy M Bialas, Lisa Stamper, Huali Wu, Margaret Gilbert, Robert Blair, Xavier Alvarez, Hannah Itell, Meng Chen, Ashlesha Deshpande, Flavia Chiuppesi, Felix Wussow, Don J Diamond, Nathan Vandergrift, Mark R Walter, Peter A Barry, Michael Cohen-Wolkowiez, Katia Koelle, Amitinder Kaur, Sallie R Permar
Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission in the setting of primary maternal infection and subsequent viremia, which is required for placental virus exposure...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28670334/evaluation-of-human-cytomegalovirus-antigen-expression-in-invasive-breast-carcinoma-in-a-population-of-iranian-patients
#9
Fereshteh Mohammadizadeh, Fatemeh Mahmudi
BACKGROUND: The role of human cytomegalovirus (HCMV) in the development of breast carcinoma is questionable. The aim of this study was to evaluate the expression of the immediate early antigen (IE) of HCMV in breast carcinoma and its association with some clinicopathologic factors in a population of Iranian patients. METHODS: Formalin-fixed and paraffin-embedded tissue blocks from the pathology laboratories of the Azahra and Shahid Beheshti hospitals, Isfahan, Iran, from 2013 to 2016, were used in the study...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28664574/the-human-cytomegalovirus-nuclear-egress-complex-unites-multiple-functions-recruitment-of-effectors-nuclear-envelope-rearrangement-and-docking-to-nuclear-capsids
#10
REVIEW
Manfred Marschall, Yves A Muller, Benedikt Diewald, Heinrich Sticht, Jens Milbradt
BACKGROUND: Nuclear replication represents a common hallmark of herpesviruses achieved by a number of sequentially unrolled regulatory processes. A rate-limiting step is provided by nucleo-cytoplasmic capsid export, for which a defined multiregulatory protein complex, namely, the nuclear egress complex (NEC), is assembled comprising both viral and cellular components. The NEC regulates at least 3 aspects of herpesviral nuclear replication: (1) multimeric recruitment of NEC-associated effector proteins, (2) reorganization of the nuclear lamina and membranes, and (3) the docking to nuclear capsids...
June 30, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/28664508/correlation-between-expression-of-recombinant-proteins-and-abundance-of-h3k4me3-on-the-enhancer-of-human-cytomegalovirus-major-immediate-early-promoter
#11
Benjamin P C Soo, Julian Tay, Shirelle Ng, Steven C L Ho, Yuansheng Yang, Sheng-Hao Chao
Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter...
August 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28663444/atomic-structure-of-the-human-cytomegalovirus-capsid-with-its-securing-tegument-layer-of-pp150
#12
Xuekui Yu, Jonathan Jih, Jiansen Jiang, Z Hong Zhou
Herpesviruses possess a genome-pressurized capsid. The 235-kilobase genome of human cytomegalovirus (HCMV) is by far the largest of any herpesvirus, yet it has been unclear how its capsid, which is similar in size to those of other herpesviruses, is stabilized. Here we report a HCMV atomic structure consisting of the herpesvirus-conserved capsid proteins MCP, Tri1, Tri2, and SCP and the HCMV-specific tegument protein pp150-totaling ~4000 molecules and 62 different conformers. MCPs manifest as a complex of insertions around a bacteriophage HK97 gp5-like domain, which gives rise to three classes of capsid floor-defining interactions; triplexes, composed of two "embracing" Tri2 conformers and a "third-wheeling" Tri1, fasten the capsid floor...
June 30, 2017: Science
https://www.readbyqxmd.com/read/28656174/human-cytomegalovirus-infected-glioblastoma-cells-display-stem-cell-like-phenotypes
#13
Che Liu, Paul A Clark, John S Kuo, Robert F Kalejta
Glioblastoma multiforme (GBM) is the most common brain tumor in adults. Human cytomegalovirus (HCMV) genomes are present in GBM tumors, yielding hope that antiviral treatments could prove therapeutic and improve the poor prognosis of GBM patients. We discovered that GBM cells infected in vitro with HCMV display properties of cancer stem cells. HCMV-infected GBM cells grow more slowly than mock-infected controls, demonstrate a higher capacity for self-renewal determined by a sphere formation assay, and display resistance to the chemotherapeutic drug temozolomide...
May 2017: MSphere
https://www.readbyqxmd.com/read/28647908/cmv-immune-evasion-and-manipulation-of-the-immune-system-with-aging
#14
REVIEW
Sarah E Jackson, Anke Redeker, Ramon Arens, Debbie van Baarle, Sara P H van den Berg, Chris A Benedict, Luka Čičin-Šain, Ann B Hill, Mark R Wills
Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response...
June 2017: GeroScience
https://www.readbyqxmd.com/read/28638769/deeper-insight-into-the-six-step-domino-reaction-of-aldehydes-with-malononitrile-and-evaluation-of-antiviral-and-antimalarial-activities-of-the-obtained-bicyclic-products
#15
Christina M Bock, Gangajji Parameshwarappa, Simon Bönisch, Walter Bauer, Corina Hutterer, Maria Leidenberger, Oliver Friedrich, Manfred Marschall, Barbara Kappes, Andreas Görling, Svetlana B Tsogoeva
The straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. An unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. Presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehydes, performing post-modifications of domino products, applying bifunctional organocatalysts and comprehensive NMR studies of selected domino products...
June 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28638004/modification-of-the-hcmv-specific-ifn-%C3%AE-release-test-quantiferon-cmv-and-a-novel-proposal-for-its-application
#16
Takahiro Kobayashi, Jun-Ichi Sato, Kazufumi Ikuta, Ryoko Kanno, Kyoko Nishiyama, Tetsuo Koshizuka, Ken Ishioka, Tatsuo Suzutani
Human cytomegalovirus (HCMV) is universally distributed among humans without any adverse effects; however, it induces severe diseases in immunocompromised patients such as organ transplant recipients and AIDS patients. To manage these immunocompromised patients, an easy clinical examination for the monitoring of disease risk is required. In this study, we modified the interferon-γ (IFN-γ) release test (QuantiFERON(®)-CMV) using HCMV immediate early-1 (IE-1) or pp65 whole proteins, or UV-inactivated HCMV particles as an antigen...
June 22, 2017: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/28637877/ex-vivo-expanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#17
Lisa L Liu, Vivien Béziat, Vincent Y S Oei, Aline Pfefferle, Marie Schaffer, Sören Lehmann, Eva Hellström-Lindberg, Stefan Söderhäll, Mats Heyman, Dan Grandér, Karl-Johan Malmberg
Manipulation of human natural killer (NK) cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIR), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637762/differential-requirement-of-human-cytomegalovirus-ul112-113-protein-isoforms-for-viral-replication
#18
Tim Schommartz, Jiajia Tang, Rebekka Brost, Wolfram Brune
The UL112-113 gene is one of the few alternatively spliced genes of human cytomegalovirus (HCMV). It codes for four phosphoproteins, p34, p43, p50, and p84, all of which are expressed with early kinetics and accumulate at sites of viral DNA replication within the host cell nucleus. Although these proteins are known to play important, possibly essential, roles in the viral replication cycle, little is known about the contribution of individual UL112-113 protein products. Here we used splice site mutagenesis, intron deletion and substitution, and nonsense mutagenesis to prevent the individual expression of each UL112-113 protein isoform and to investigate the importance of each isoform for viral replication...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28628650/the-human-cytomegalovirus-glycoprotein-pul11-acts-via-cd45-to-induce-t-cell-il-10-secretion
#19
Jasmin Zischke, Panagiota Mamareli, Claudia Pokoyski, Ildar Gabaev, Sabine Buyny, Roland Jacobs, Christine S Falk, Matthias Lochner, Tim Sparwasser, Thomas F Schulz, Penelope C Kay-Fedorov
Human Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host's immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28621685/active-evolution-of-memory-b-cells-specific-to-viral-gh-gl-pul128-130-131-pentameric-complex-in-healthy-subjects-with-silent-human-cytomegalovirus-infection
#20
Lin Xia, Aimin Tang, Weixu Meng, Daniel C Freed, Linling He, Dai Wang, Fengsheng Li, Leike Li, Wei Xiong, Xun Gui, Robbie D Schultz, Haotai Chen, Xi He, Ryan Swoyer, Sha Ha, Yaping Liu, Charles D Morris, Yu Zhou, I-Ming Wang, Qinjian Zhao, Wenxin Luo, Ningshao Xia, Amy S Espeseth, Daria J Hazuda, Richard E Rupp, Alan D Barrett, Ningyan Zhang, Jiang Zhu, Tong-Ming Fu, Zhiqiang An
Human cytomegalovirus (HCMV) can cause life-threatening infection in immunosuppressed patients, and in utero infection that may lead to birth defects. No vaccine is currently available. HCMV infection in healthy subjects is generally asymptomatic, and virus persists as latent infection for life. Host immunity is effective against reactivation and super-infection with another strain. Thus, vaccine candidates able to elicit immune responses similar to those of natural infection may confer protection. Since neutralization is essential for prophylactic vaccines, it is important to understand how antiviral antibodies are developed in natural infection...
June 3, 2017: Oncotarget
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