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https://www.readbyqxmd.com/read/27926930/cytomegalovirus-specific-il-10-producing-cd4-t-cells-are-governed-by-type-i-ifn-induced-il-27-and-promote-virus-persistence
#1
Mathew Clement, Morgan Marsden, Maria A Stacey, Juneid Abdul-Karim, Silvia Gimeno Brias, Diana Costa Bento, Martin J Scurr, Peter Ghazal, Casey T Weaver, Gianluca Carlesso, Simon Clare, Simon A Jones, Andrew Godkin, Gareth W Jones, Ian R Humphreys
CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27913630/adaptive-nkg2c-nk-cell-response-and-the-risk-of-cytomegalovirus-infection-in-kidney-transplant-recipients
#2
Dolores Redondo-Pachón, Marta Crespo, Jose Yélamos, Aura Muntasell, María José Pérez-Sáez, Silvia Pérez-Fernández, Joan Vila, Carlos Vilches, Julio Pascual, Miguel López-Botet
CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C(+) NK cells. The distribution of NKG2C(+) NK cells and NKG2C genotypes (NKG2C(+/+), NKG2C(+/del), NKG2C(del/del)) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts...
December 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27912771/a-dna-vaccine-encoding-the-viral-hemorrhagic-septicemia-virus-genotype-ivb-glycoprotein-confers-protection-in-muskellunge-esox-masquinongy-rainbow-trout-oncorhynchus-mykiss-brown-trout-salmo-trutta-and-lake-trout-salvelinus-namaycush
#3
Isaac F Standish, Elena V Millard, Travis O Brenden, Mohamed Faisal
BACKGROUND: The viral hemorrhagic septicemia virus (VHSV) is one of the most serious fish pathogens. In 2003, a novel sublineage (genotype IVb) of this deadly virus emerged in the Great Lakes basin causing serious fish kills. We have previously demonstrated that a DNA plasmid (pcDNA), containing a cytomegalovirus (CMV) promoter and the viral hemorrhagic septicemia virus (VHSV) genotype IVb glycoprotein (G) gene insert (designated pVHSivb-G) confers moderate protection in muskellunge (Esox masquinongy), a highly susceptible species upon challenge...
December 2, 2016: Virology Journal
https://www.readbyqxmd.com/read/27901409/a-non-invasive-in-vitro-monitoring-system-reporting-skeletal-muscle-differentiation
#4
Deniz Öztürk-Kaloglu, David Hercher, Philipp Heher, Katja Posa-Markaryan, Simon Sperger, Alice Zimmermann, Susanne Wolbank, Heinz Redl, Ara Hacobian
Monitoring of cell differentiation is a crucial aspect of cell-based therapeutic strategies depending on tissue maturation. In this study we have developed a non-invasive reporter system to trace murine skeletal muscle differentiation. Either a secreted bioluminescent reporter (Metridia luciferase) or a fluorescent reporter (GFP) was placed under the control of the truncated muscle creatine kinase (MCK) basal promoter enhanced by variable numbers of upstream MCK E-boxes. The engineered pE3MCK vector, coding a triple tandem of E-Boxes and the truncated MCK promoter, showed 20-fold higher levels of luciferase activation compared to a CMV promoter...
November 30, 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27883971/2-3-7-8-tetrachlorodibenzo-p-dioxin-and-the-viral-infection
#5
REVIEW
Filomena Fiorito, Rita Santamaria, Carlo Irace, Luisa De Martino, Giuseppe Iovane
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread highly toxic environmental contaminant, suppresses immune response and leads to an increased susceptibility to infectious agents. In particular, several studies have provided evidence that TCDD decreases resistance to numerous viruses. Indeed, in vivo and in vitro investigations showed that the presence of TCDD is able to interfere with the replication of both human and animal viruses, such as influenza A viruses, coxsackie virus B3, immunodeficiency virus type-1 (HIV-1), cytomegalovirus (CMV), herpes simplex II, and bovine herpesvirus 1...
November 21, 2016: Environmental Research
https://www.readbyqxmd.com/read/27878291/adenovirus-mediated-truncated-bid-overexpression-induced-by-the-cre-loxp-system-promotes-the-cell-apoptosis-of-cd133-ovarian-cancer-stem-cells
#6
Qifang Long, Ru Yang, Weixian Lu, Weipei Zhu, Jundong Zhou, Cui Zheng, Dongmei Zhou, Ling Yu, Jinchang Wu
Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells...
November 21, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27867348/better-targeting-better-efficiency-for-wide-scale-neuronal-transduction-with-the-synapsin-promoter-and-aav-php-b
#7
Kasey L Jackson, Robert D Dayton, Benjamin E Deverman, Ronald L Klein
Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27859428/low-p16-ink4a-expression-in-early-passage-human-prostate-basal-epithelial-cells-enables-immortalization-by-telomerase-expression-alone
#8
Mindy Kim Graham, Lorenzo Principessa, Lizamma Antony, Alan K Meeker, John T Isaacs
BACKGROUND: There are two principal senescence barriers that must be overcome to successfully immortalize primary human epithelial cells in culture, stress-induced senescence, and replicative senescence. The p16(INK4a) /retinoblastoma protein (p16/Rb) pathway mediates stress-induced senescence, and is generally upregulated by primary epithelial cells in response to the artificial conditions from tissue culture. Replicative senescence is associated with telomere loss. Following each round of cell division, telomeres progressively shorten...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27854310/does-herd-immunity-exist-in-aquatic-animals
#9
Isaac F Standish, Travis O Brenden, Mohamed Faisal
Viral hemorrhagic septicemia virus genotype IVb (VHSV-IVb) is presently found throughout the Laurentian Great Lakes region of North America. We recently developed a DNA vaccine preparation containing the VHSV-IVb glycoprotein (G) gene with a cytomegalovirus (CMV) promoter that proved highly efficacious in protecting muskellunge (Esox masquinongy) and three salmonid species. This study was conducted to determine whether cohabitation of VHSV-IVb immunized fishes could confer protection to non-vaccinated (i.e...
November 15, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27852956/preparation-for-a-first-in-man-lentivirus-trial-in-patients-with-cystic-fibrosis
#10
Eric W F W Alton, Jeffery M Beekman, A Christopher Boyd, June Brand, Marianne S Carlon, Mary M Connolly, Mario Chan, Sinead Conlon, Heather E Davidson, Jane C Davies, Lee A Davies, Johanna F Dekkers, Ann Doherty, Sabrina Gea-Sorli, Deborah R Gill, Uta Griesenbach, Mamoru Hasegawa, Tracy E Higgins, Takashi Hironaka, Laura Hyndman, Gerry McLachlan, Makoto Inoue, Stephen C Hyde, J Alastair Innes, Toby M Maher, Caroline Moran, Cuixiang Meng, Michael C Paul-Smith, Ian A Pringle, Kamila M Pytel, Andrea Rodriguez-Martinez, Alexander C Schmidt, Barbara J Stevenson, Stephanie G Sumner-Jones, Richard Toshner, Shu Tsugumine, Marguerite W Wasowicz, Jie Zhu
We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. In preparation for a first-in-man CF trial using the lentiviral vector, we have undertaken key translational preclinical studies...
November 16, 2016: Thorax
https://www.readbyqxmd.com/read/27846155/effect-of-ex-vivo-expanded-recipient-regulatory-t-cells-on-hematopoietic-chimerism-and-kidney-allograft-tolerance-across-mhc-barriers-in-cynomolgus-macaques
#11
Raimon Duran-Struuck, Hugo P Sondermeijer, Leo Bühler, Paula Alonso-Guallart, Jonah Zitsman, Yojiro Kato, Anette Wu, Alicia N McMurchy, David Woodland, Adam Griesemer, Mercedes Martinez, Svetlan Boskovic, Tatsuo Kawai, A Benedict Cosimi, Cheng-Shie Wuu, Andrea Slate, Markus Mapara, Sam Baker, Rafal Tokarz, Vivette Dʼ Agati, Scott Hammer, Marcus Pereira, W Ian Lipkin, Thomas Wekerle, Megan Levings, Megan Sykes
BACKGROUND: Infusion of recipient regulatory T cells (Treg) promotes durable mixed hematopoietic chimerism and allograft tolerance in mice receiving allogeneic BMT with minimal conditioning. We applied this strategy in a Cynomolgus macaque model. METHODS: CD4+CD25high Treg that were polyclonally expanded in culture were highly suppressive in vitro and maintained high expression of FoxP3. Eight monkeys underwent nonmyeloablative conditioning and MHC-mismatched BMT with or without Treg infusion...
November 15, 2016: Transplantation
https://www.readbyqxmd.com/read/27842439/stable-in-vivo-transgene-expression-in-endothelial-cells-with-helper-dependent-adenovirus-roles-of-promoter-and-interleukin-10
#12
Nagadhara Dronadula, Bradley Wacker, Reginald Van Der Kwast, Jingwan Zhang, David A Dichek
Our long-term goal is to prevent or reverse atherosclerosis by delivering gene therapy from stably transduced endothelial cells (EC). We previously reported that EC-directed gene therapy with a helper-dependent adenovirus (HDAd) expressing apolipoprotein A-I (apo A-I) retarded development of atherosclerosis in rabbit carotid arteries over a 1-month interval. However, a 70% decline in apo A-I expression during this time raised concerns about long-term efficacy of this approach. Here we report use of several approaches aimed either at preventing this decline or at increasing apo A-I expression from HDAd at all time points: codon optimization, deletion of 3´ untranslated sequences, substitution of a synthetic mammalian-based promoter (4XETE) for the CMV promoter, and co-transduction with an HDAd expressing interleukin-10...
November 14, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27834948/the-antitumor-efficacy-of-anti-p21ras-scfv-mediated-by-the-dual-promoter-regulated-recombinant-adenovirus-kghv300
#13
X Pan, X Liu, J Li, S Zhen, D Liu, Q Feng, W Zhao, Y Luo, Y Zhang, H Li, J Yang
Ras mutations and overexpression of the Ras protein; i.e., p21Ras, are main causes of cancer development and progression, which has made the Ras gene and p21Ras important targets for therapy of Ras-driven cancers. We previously prepared recombinant adenovirus KGHV100 based on replication-defective adenovirus type 5, which could intracellularly express anti-p21Ras single chain fragment viable antibodies (scFv) and repress tumor growth in vitro and in vivo. However, the anti-tumor effects of this anti-p21Ras scFv were limited by short-term scFv expression due to a replication defect of KGHV100...
November 11, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27832434/monitoring-of-venus-transgenic-cell-migration-during-pregnancy-in-non-transgenic-rabbits
#14
N Lipták, O I Hoffmann, A Kerekes, G Iski, D Ernszt, K Kvell, L Hiripi, Z Bősze
Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken ß-actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system...
November 10, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27824944/human-cytomegalovirus-mir-ul148d-facilitates-latent-viral-infection-by-targeting-host-cell-immediate-early-response-gene-5
#15
Chaoyun Pan, Dihan Zhu, Yan Wang, Limin Li, Donghai Li, Fenyong Liu, Chen-Yu Zhang, Ke Zen
The mechanisms underlying human cytomegalovirus (HCMV) latency remain incompletely understood. Here, we showed that a HCMV-encoded miRNA, miR-UL148D, robustly accumulates during late stages of experimental latent HCMV infection in host cells and promotes HCMV latency by modulating the immediate early response gene 5 (IER5)-cell division cycle 25B (CDC25B) axis in host cells. miR-UL148D inhibited IER5 expression by directly targeting the three-prime untranslated region(3'UTR) of IER5 mRNA and thus rescued CDC25B expression during the establishment of viral latency...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27799777/high-frequency-oscillatory-ventilation-is-an-effective-treatment-for-severe-pediatric-acute-respiratory-distress-syndrome-with-refractory-hypoxemia
#16
Yu-Xiong Guo, Zhao-Ni Wang, Ya-Ting Li, Li Pan, Li-Fen Yang, Yan Hu, Yue-Yu Sun, Liang-Ming Cai, Zhuang-Gui Chen
BACKGROUND AND PURPOSE: Early or primary application of high-frequency oscillatory ventilation (HFOV) has been recently suggested not to offer benefit to patients with acute respiratory distress syndrome (ARDS). However, the rescue effects of HFOV on severe pediatric acute respiratory distress syndrome (PARDS) with hypoxemia refractory to conventional mechanical ventilation (CMV) remain unclear. This study aimed to determine whether severe PARDS children would benefit from HFOV when oxygenation deteriorated on CMV and to identify any potential risk factors related to mortality...
2016: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/27799472/empower-multiplex-cell-and-tissue-specific-crispr-mediated-gene-manipulation-with-self-cleaving-ribozymes-and-trna
#17
Li Xu, Lixia Zhao, Yandi Gao, Jing Xu, Renzhi Han
Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system has emerged in recent years as a highly efficient RNA-guided gene manipulation platform. Simultaneous editing or transcriptional activation/suppression of different genes becomes feasible with the co-delivery of multiple guide RNAs (gRNAs). Here, we report that multiple gRNAs linked with self-cleaving ribozymes and/or tRNA could be simultaneously expressed from a single U6 promoter to exert genome editing of dystrophin and myosin binding protein C3 in human and mouse cells...
October 30, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27783035/the-microtubule-inhibitor-podofilox-inhibits-an-early-entry-step-of-human-cytomegalovirus
#18
Tobias Cohen, Toni M Schwarz, Frederic Vigant, Thomas J Gardner, Rosmel E Hernandez, Benhur Lee, Domenico Tortorella
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface...
October 24, 2016: Viruses
https://www.readbyqxmd.com/read/27777581/trichoderma-harzianum-t-22-induces-systemic-resistance-in-tomato-infected-by-cucumber-mosaic-virus
#19
Antonella Vitti, Elisa Pellegrini, Cristina Nali, Stella Lovelli, Adriano Sofo, Maria Valerio, Antonio Scopa, Maria Nuzzaci
Understanding the induction of plant defenses against viruses using biocontrol agents is essential for developing new strategies against these pathogens, given the ineffectiveness of chemical treatments. The ability of Trichoderma harzianum, strain T-22 (T22) to control Cucumber mosaic virus (CMV) in Solanum lycopersicum var. cerasiforme plants and the changes in the physiology of tomato treated/infected with T22/CMV were examined. Plant growth-promoting effects, photosynthetic performance, reactive oxygen species scavenging enzymes, and phytohormones were investigated...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27777041/cytomegalovirus-as-an-oncomodulatory-agent-in-the-progression-of-glioma
#20
Gabriel P Joseph, Ryan McDermott, Maria A Baryshnikova, Charles S Cobbs, Ilya V Ulasov
Glioblastoma multiforme (GBM) is the most aggressive neoplastic brain tumor in humans with a median survival of less than 2 years. It is therefore critical to understand the mechanism of glioma progression and to identify future targets for intervention. We investigate the mechanisms of cytomegalovirus as an oncomodulatory agent implicated in glioma progression, as well as immunosuppression. This review provides a comprehensive evaluation of recent investigative developments concerning the role of CMV in cellular processes during glioma growth...
October 21, 2016: Cancer Letters
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