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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
#1
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
#2
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-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#3
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human 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 (KIRs), 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
#4
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
#5
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 19, 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
#6
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
https://www.readbyqxmd.com/read/28615204/human-cytomegalovirus-ie2-protein-disturbs-brain-development-by-dysregulating-neural-stem-cell-maintenance-and-the-polarization-of-migrating-neurons
#7
Dasol Han, Sung-Hyun Byun, Juwan Kim, Mookwang Kwon, Samuel J Pleasure, Jin-Hyun Ahn, Keejung Yoon
Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells in vitro, indicating reduction of self-renewal and expansion of neural progenitors by IE2...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28595965/low-expression-of-estrogen-receptor-%C3%AE-and-progesterone-receptor-in-human-breast-cancer-tissues-is-associated-with-high-grade-human-cytomegalovirus-protein-expression
#8
Afsar Rahbar, Joel Touma, Helena Costa, Belghis Davoudi, Ida Rashid Bukholm, Torill Sauer, Katja Vetvik, Jürgen Geisler, Cecilia Söderberg-Naucler
BACKGROUND: The underlying mechanisms for breast cancer (BC) are largely unknown. We investigated possible correlations between the expression levels of human cytomegalovirus (HCMV) proteins and established histopathological markers of BC, including expression of estrogen receptor (ER)-α, the progesterone receptor (PgR), and HER2. MATERIALS AND METHODS: We retrospectively examined paraffin-embedded biopsy specimens of BC (n = 62), ductal carcinoma in situ (n = 19), and adjacent normal breast tissue (n = 42) for HCMV immediate-early protein (IE), HCMV late antigen, HCMV DNA and RNA, and investigated possible correlations between them and expression of ER-α, PgR, and HER2...
May 11, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28594901/detection-of-human-cytomegalovirus-in-glioblastoma-among-taiwanese-subjects
#9
Ching-Fen Yang, Hsiang-Ling Ho, Shih-Chieh Lin, Chih-Yi Hsu, Donald Ming-Tak Ho
The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) has been debated for more than a decade. We investigated the presence of HCMV genes, RNA and protein in GBMs and their relationships with tumor progression. Results of quantitative PCR for HCMV UL73, nested PCR for HCMV UL144, in situ hybridization (ISH) for RNA transcript, and immunohistochemistry (IHC) for protein expression and their relationship to the prognosis of 116 patients with GBM were evaluated. Nine (7.8%) cases revealed a low concentration of HCMV UL73, and only 2 of the 9 (1...
2017: PloS One
https://www.readbyqxmd.com/read/28592251/distinct-expression-profile-of-hcmv-encoded-mirnas-in-plasma-from-oral-lichen-planus-patients
#10
Meng Ding, Xiang Wang, Cheng Wang, Xiaoshuang Liu, Ke Zen, Wenmei Wang, Chen-Yu Zhang, Chunni Zhang
BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated autoimmune disease. The aetiology and molecular mechanisms of OLP remain unclear. Human cytomegalovirus (HCMV) infection is a causal factor in the development of various diseases, but the clinical relevance of HCMV in OLP has not been thoroughly investigated. METHODS: In the present study, we firstly examined twenty-three HCMV-encoded microRNA (miRNA) expression profiles in plasma from training set that including 21 OLP patients and 18 healthy controls using RT-qPCR technology...
June 7, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28589873/human-cytomegalovirus-micrornas-are-carried-by-virions-and-dense-bodies-and-are-delivered-to-target-cells
#11
Abdul-Aleem Mohammad, Helena Costa, Natalia Landázuri, Weng-Onn Lui, Kjell Hultenby, Afsar Rahbar, Koon-Chu Yaiw, Cecilia Söderberg-Nauclér
Human cytomegalovirus (HCMV) infection results in the production of virions, dense bodies (DBs) and non-infectious enveloped particles, all of which incorporate proteins and RNAs that can be transferred to host cells. Here, we investigated whether virions and DBs also carry microRNAs (miRNAs) and assessed their delivery and functionality in cells. Human lung fibroblasts (MRC-5) were infected with the HCMV strain AD169, and conditioned cell culture medium was collected and centrifuged. The pellets were treated with RNase-ONE, and the virions and DBs were purified with a potassium tartrate-glycerol gradient and dialysed...
May 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28588572/positively-selected-sites-at-hcmv-gb-furin-processing-region-and-their-effects-in-cleavage-efficiency
#12
Lucas M Stangherlin, Felipe N de Paula, Marcelo Y Icimoto, Leonardo G P Ruiz, Maurício L Nogueira, Antônio S K Braz, Luiz Juliano, Maria C C da Silva
Human cytomegalovirus is a ubiquitous infectious agent that affects mainly immunosuppressed, fetuses, and newborns. The virus has several polymorphic regions, in particular in the envelope glycoproteins. The UL55 gene encodes the glycoprotein B that has a variable region, containing a furin cleavage site and according to the variability different genotypes are characterized. Here we investigated variability and existence of selective pressure on the UL55 variable region containing the furin cleavage site in 213 clinical sequences from patients worldwide...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28578521/mir-138-promotes-migration-and-tube-formation-of-human-cytomegalovirus-infected-endothelial-cells-through-the-sirt1-p-stat3-pathway
#13
Shanchao Zhang, Lei Liu, Ruijin Wang, Houzhen Tuo, Yanjun Guo, Li Yi, Dexin Wang, Jiawei Wang
Human cytomegalovirus (HCMV) has been reported to be linked to vascular disease through the induction of neovessel formation. We have previously reported that microRNA (miR)-217 and miR-199a-5p enhance endothelial angiogenesis via inhibition of sirtuin 1 (SIRT1) in HCMV-infected human umbilical vein endothelial cells (HUVECs). Here, we found that miR-138 also suppressed the expression of the SIRT1 protein and stimulated phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). Moreover, the regulation of p-STAT3 expression mediated by SIRT1 was found to promote HCMV-induced angiogenesis...
June 3, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28570668/cooperative-inhibition-of-rip1-mediated-nf-%C3%AE%C2%BAb-signaling-by-cytomegalovirus-encoded-deubiquitinase-and-inactive-homolog-of-cellular-ribonucleotide-reductase-large-subunit
#14
Ki Mun Kwon, Se Eun Oh, Young Eui Kim, Tae-Hee Han, Jin-Hyun Ahn
Several viruses have been found to encode a deubiquitinating protease (DUB). These viral DUBs are proposed to play a role in regulating innate immune or inflammatory signaling. In human cytomegalovirus (HCMV), the largest tegument protein encoded by UL48 contains DUB activity, but its cellular targets are not known. Here, we show that UL48 and UL45, an HCMV-encoded inactive homolog of cellular ribonucleotide reductase (RNR) large subunit (R1), target receptor-interacting protein kinase 1 (RIP1) to inhibit NF-κB signaling...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28567162/cytomegalovirus-macrophages-and-breast-cancer
#15
REVIEW
S Pasquereau, F Al Moussawi, W Karam, M Diab Assaf, A Kumar, G Herbein
The human cytomegalovirus (HCMV) is a betaherpesvirus that is highly host specific, infects among others epithelial cells and macrophages, and has been recently mentioned as having oncomodulatory properties. HCMV is detected in the breast tumor tissue where macrophages, especially tumor associated macrophages, are associated with a poor prognosis. In this review, we will discuss the potential implication of HCMV in breast cancer with emphasis on the role played by macrophages.
2017: Open Virology Journal
https://www.readbyqxmd.com/read/28567042/hepatitis-c-virus-and-human-cytomegalovirus-natural-killer-cell-subsets-in-persistent-viral-infections
#16
REVIEW
Julia Pollmann, Alexander Rölle, Maike Hofmann, Adelheid Cerwenka
Hepatitis C virus (HCV) and human cytomegalovirus (HCMV) are prominent examples of RNA and DNA viruses, respectively, that establish a persistent infection in their host. HCV affects over 185 million patients worldwide, who are at high risk for developing liver fibrosis, liver cirrhosis, and ultimately hepatocellular carcinoma. Recent breakthroughs in HCV therapy, using direct-acting antivirals have provided the opportunity to monitor natural killer (NK) cells after clearance of a chronic infection. There is now increasing evidence that the individual NK cell repertoire before infection is predictive for the course of disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28566275/fibroblast-adapted-human-cmv-vaccines-elicit-predominantly-conventional-cd8-t-cell-responses-in-humans
#17
Susan E Murray, Pavlo A Nesterenko, Adam L Vanarsdall, Michael W Munks, Savannah M Smart, Eren M Veziroglu, Lavinia C Sagario, Ronzo Lee, Frans H J Claas, Ilias I N Doxiadis, Michael A McVoy, Stuart P Adler, Ann B Hill
Cytomegalovirus (CMV)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of vaccinated monkeys to clear a subsequent virulent simian immunodeficiency virus challenge. The protective vaccine elicited unconventional CD8 T cell responses that were entirely restricted by MHC II or the nonclassical MHC I molecule, MHC-E. These unconventional responses were only elicited by a fibroblast-adapted rhesus CMV vector with limited tissue tropism; a repaired vector with normal tropism elicited conventional responses...
May 31, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28554666/human-cytomegalovirus-mediated-immunomodulation-effects-on-glioblastoma-progression
#18
REVIEW
Haidn Foster, Ilya V Ulasov, Charles S Cobbs
The presence of human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM), first established in 2002, has developed into an area of considerable interest and controversy. Numerous studies have found evidence of possible HCMV infection of GBM tumor cells as well as myriad onco- and immunomodulatory properties exhibited by HCMV antigens and transcripts, while recent reports have failed to detect HCMV particles in GBM and question the virus' role in tumor progression. This review highlights the known immunomodulatory properties of HCMV, independent of GBM infection status, that help drive the virus from peripheral blood into the vital tissues and subsequently dampen local immune response, assisting GBM tumors in evading immune surveillance and contributing to the disease's poor prognosis...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28533400/the-pentameric-complex-drives-immunologically-covert-cell-cell-transmission-of-wild-type-human-cytomegalovirus
#19
Isa Murrell, Carmen Bedford, Kristin Ladell, Kelly L Miners, David A Price, Peter Tomasec, Gavin W G Wilkinson, Richard J Stanton
Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation with a virus that retained a clinically relevant phenotype, we reconstructed a wild-type (WT) HCMV genome using bacterial artificial chromosome technology. Like clinical virus, this genome proved to be unstable in cell culture; however, propagation of intact virus was achieved by placing the RL13 and UL128 genes under conditional expression...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28523518/decreased-human-leukocyte-antigen-a-02-01-frequency-is-associated-with-risk-of-glioma-and-existence-of-human-cytomegalovirus-a-case-control-study-in-northern-china
#20
Sheng Han, Jian Deng, Zixun Wang, Huan Liu, Wen Cheng, Anhua Wu
BACKGROUND: Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. METHODS: The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender...
May 18, 2017: Cancer Immunology, Immunotherapy: CII
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