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https://www.readbyqxmd.com/read/28096485/murine-cytomegalovirus-deubiquitinase-regulates-viral-chemokine-levels-to-control-inflammation-and-pathogenesis
#1
Adam T Hilterbrand, Daniel R Boutz, Edward M Marcotte, Jason W Upton
: Maintaining control over inflammatory processes represents a paradox for viral pathogens. Although many viruses induce host inflammatory responses to facilitate infection, control is necessary to avoid overactivation. One way is through the manipulation of proinflammatory chemokine levels, both host and viral. Murine cytomegalovirus (MCMV), a model betaherpesvirus, encodes a viral C-C chemokine, MCK2, which promotes host inflammatory responses and incorporates into virions to facilitate viral dissemination...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28079113/congenital-hearing-loss
#2
Anna M H Korver, Richard J H Smith, Guy Van Camp, Mark R Schleiss, Maria A K Bitner-Glindzicz, Lawrence R Lustig, Shin-Ichi Usami, An N Boudewyns
Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss...
January 12, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28072927/artificial-induction-of-native-aquaporin-1-expression-in-human-salivary-cells
#3
Z Wang, S Pradhan-Bhatt, M C Farach-Carson, M J Passineau
Gene therapy for dry mouth disorders has transitioned in recent years from theoretical to clinical proof of principle with the publication of a first-in-man phase I/II dose escalation clinical trial in patients with radiation-induced xerostomia. This trial used a prototype adenoviral vector to express aquaporin-1 (AQP1), presumably in the ductal cell layer and/or in surviving acinar cells, to drive transcellular flux of interstitial fluid into the labyrinth of the salivary duct. As the development of this promising gene therapy continues, safety considerations are a high priority, particularly those that remove nonhuman agents (i...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28069101/immune-responses-in-mice-vaccinated-with-a-dna-vaccine-expressing-serine-protease-like-protein-from-the-new-born-larval-stage-of-trichinella-spiralis
#4
Jing Xu, Xue Bai, Li Bo Wang, Hai Ning Shi, Joke W B VAN DER Giessen, Pascal Boireau, Ming Yuan Liu, Xiao Lei Liu
Trichinella spiralis is a parasitic helminth that can infect almost all mammals, including humans. Trichinella spiralis infection elicits a typical type 2 immune responses, while suppresses type 1 immune responses, which is in favour of their parasitism. DNA vaccines have been shown to be capable of eliciting balanced CD4+ and CD8+ T cell responses as well as humoral immune responses in small-animal models, which will be advantage to induce protective immune response against helminth infection. In this study, serine protease (Ts-NBLsp) was encoded by a cDNA fragment of new-born T...
January 10, 2017: Parasitology
https://www.readbyqxmd.com/read/28060929/a-single-vector-platform-for-high-level-gene-transduction-of-central-neurons-adeno-associated-virus-vector-equipped-with-the-tet-off-system
#5
Jaerin Sohn, Megumu Takahashi, Shinichiro Okamoto, Yoko Ishida, Takahiro Furuta, Hiroyuki Hioki
Visualization of neurons is indispensable for the investigation of neuronal circuits in the central nervous system. Virus vectors have been widely used for labeling particular subsets of neurons, and the adeno-associated virus (AAV) vector has gained popularity as a tool for gene transfer. Here, we developed a single AAV vector Tet-Off platform, AAV-SynTetOff, to improve the gene-transduction efficiency, specifically in neurons. The platform is composed of regulator and response elements in a single AAV genome...
2017: PloS One
https://www.readbyqxmd.com/read/28060895/a-luciferase-gene-driven-by-an-alphaherpesviral-promoter-also-responds-to-immediate-early-antigens-of-the-betaherpesvirus-hcmv-allowing-comparative-analyses-of-different-human-herpesviruses-in-one-reporter-cell-line
#6
Anna Katharina Maier, Raimund Jung, Clarissa Villinger, Axel Schubert, Paul Walther, Christian Sinzger, Diana Lieber
Widely used methods for quantification of human cytomegalovirus (HCMV) infection in cell culture such as immunoblotting or plaque reduction assays are generally restricted to low throughput and require time-consuming evaluation. Up to now, only few HCMV reporter cell lines have been generated to overcome these restrictions and they are afflicted with other limitations because permanently expandable cell lines are normally not fully permissive to HCMV. In this work, a previously existing epithelial cell line hosting a luciferase gene under control of a Varicella-zoster virus promoter was adopted to investigate HCMV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28042541/rational-development-of-a-polycistronic-plasmid-with-a-cpg-free-bacterial-backbone-as-a-potential-tool-for-direct-reprogramming
#7
Kianoush Dormiani, Hamid Mir Mohammad Sadeghi, Hojjat Sadeghi-Aliabadi, Mahboobeh Forouzanfar, Hossein Baharvand, Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani
OBJECTIVE: Induced pluripotent stem cells are generated from somatic cells by direct reprogramming. These reprogrammed pluripotent cells have different applications in biomedical fields such as regenerative medicine. Although viral vectors are widely used for efficient reprogramming, they have limited applications in the clinic due to the risk for immunogenicity and insertional mutagenesis. Accordingly, we designed and developed a small, non-integrating plasmid named pLENSO/Zeo as a 2A-mediated polycistronic expression vector...
2017: Cell Journal
https://www.readbyqxmd.com/read/28028680/establishment-of-mouse-leukemia-cell-lines-expressing-human-cd4-ccr5-using-lentiviral-vectors
#8
Ya-Jing Li, Fu-Yan ZhuGe, Chang-Chun Zeng, Jin-Yang He, Ning Tan, Juan Liang
A low-cost rodent model of HIV infection and which presents high application value is an effective tool to investigate HIV infection and pathogenesis. However, development of such a small animal model has been hampered by the unsuitability of rodent cells for HIV-1 replication given that the retrovirus HIV-1 has high selectivity to its host cell. Our study used the mouse leukemia cell lines L615 and L1210 that were induced by murine leukemia virus and transfected with hCD4/CCR5 loaded-lentiviral vector. Lentiviral vectors containing the genes hCD4/CCR5 under the transcriptional control of cytomegalovirus promoter were designed...
December 28, 2016: Virus Genes
https://www.readbyqxmd.com/read/28017761/tenofovir-alafenamide-demonstrates-broad-cross-genotype-activity-against-wild-type-hbv-clinical-isolates-and-maintains-susceptibility-to-drug-resistant-hbv-isolates-in%C3%A2-vitro
#9
Yang Liu, Michael D Miller, Kathryn M Kitrinos
Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV). This study evaluated the antiviral activity of TAF against wild-type genotype A-H HBV clinical isolates as well as adefovir-resistant, lamivudine-resistant, and entecavir-resistant HBV isolates. Full length HBV genomes or the polymerase/reverse transcriptase (pol/RT) region from treatment-naïve patients infected with HBV genotypes A-H were amplified and cloned into an expression vector under the control of a CMV promoter. In addition, 11 drug resistant HBV constructs were created by site-directed mutagenesis of a full length genotype D construct...
December 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/28013079/development-of-dual-fluorescence-cell-based-biosensors-for-detecting-the-influence-of-environmental-factors-on-nanoparticle-toxicity
#10
Junting Liang, Xuanyu Wang, Luzhi Li, Shengmin Xu, Jiang Jiang, Lijun Wu, Guoping Zhao, Shaopeng Chen
With the expanding use of engineered nanoparticles (NPs), development of a high-throughput, sensitive method for evaluating NP safety is important. In this study, we developed cell-based biosensors to efficiently and conveniently monitor NP toxicity. The biosensor cells were obtained by transiently transfecting human cells with biosensor plasmids containing a mCherry gene regulated by an inducible promoter [an activator protein 1 (AP-1) promoter, an interleukin 8 (IL8) promoter, or a B cell translocation gene 2 (BTG2) promoter], with an enhanced green-fluorescent protein gene driven by the cytomegalovirus promoter as the internal control...
December 18, 2016: Chemosphere
https://www.readbyqxmd.com/read/28004977/establishment-of-transgenic-porcine-fibroblasts-expressing-a-human-klotho-gene-and-its-effects-on-gene-expression-and-preimplantation-development-of-cloned-embryos
#11
Sanghoon Lee, Joon Ho Moon, Kilyoung Song, Anukul Taweechaipaisankul, Young Kwang Jo, Hyun Ju Oh, Se Chang Park, Byeong Chun Lee
Even though the functions of the klotho gene in aging of small animals such as mice have been well investigated, studies using large animal models such as pigs, which have many similarities to humans, have been limited due to the absence of cell lines or animal models. Therefore, the objective of this study was to generate porcine cell lines overexpressing human klotho (hKlotho) and tetracycline (Tet)-inducible hKlotho and to produce cloned embryos from these cell lines. We designed vectors for hKlotho overexpression (CA-Klotho) under control of CMV enhancer/chicken β-actin (CAG) promoter and Tet-inducible hKlotho overexpression (Tet-Klotho, under control of doxycycline-dependent promoter)...
January 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/27999194/radiation-induced-sod2-overexpression-sensitizes-colorectal-cancer-to-radiation-while-protecting-normal-tissue
#12
Zhiqiang Zhang, Jinyi Lang, Zhi Cao, Rong Li, Xingyong Wang, Weidong Wang
This study investigated whether radiation-induced overexpression of superoxide dismutase 2 (SOD2) exerts radio-sensitizing effects on tumor cells while having radio-protective effects on normal cells during radio-activated gene therapy for human colorectal cancer. A chimeric promoter, C9BC, was generated by directly linking nine tandem CArG boxes to a CMV basic promoter, after which lentiviral vectors containing GFP and SOD2 gene driven by the C9BC promoter were constructed. Stably transfected HT-29 colorectal cancer cells and CCD 841 CoN normal colorectal cells were irradiated to a dose of 6-Gy, and cell proliferation and apoptosis were observed...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27982344/early-open-lung-ventilation-improves-clinical-outcomes-in-patients-with-left-cardiac-dysfunction-undergoing-off-pump-coronary-artery-bypass-a-randomized-controlled-trial
#13
Douglas W Bolzan, Walter José Gomes, Isadora S Rocco, Marcela Viceconte, Mara L S Nasrala, Hayanne O Pauletti, Rita Simone L Moreira, Nelson A Hossne, Ross Arena, Solange Guizilini
Objective: To compare pulmonary function, functional capacity and clinical outcomes amongst three groups of patients with left ventricular dysfunction following off-pump coronary artery bypass, namely: 1) conventional mechanical ventilation (CMV); 2) late open lung strategy (L-OLS); and 3) early open lung strategy (E-OLS). Methods: Sixty-one patients were randomized into 3 groups: 1) CMV (n=21); 2) L-OLS (n=20) initiated after intensive care unit arrival; and 3) E-OLS (n=20) initiated after intubation...
September 2016: Brazilian Journal of Cardiovascular Surgery
https://www.readbyqxmd.com/read/27974558/mechanism-of-pkr-inhibition-by-human-cytomegalovirus-ptrs1
#14
Heather A Vincent, Benjamin Ziehr, Nathaniel J Moorman
: Double stranded RNAs (dsRNA) produced during human cytomegalovirus (HCMV) infection activate the antiviral kinase PKR, which potently inhibits virus replication. The HCMV pTRS1 and pIRS1 proteins antagonize PKR to promote HCMV protein synthesis and replication, however the mechanism by which pTRS1 inhibits PKR is unclear. PKR activation occurs in a three-step cascade. First, binding to dsRNA triggers PKR homodimerizaton. PKR dimers then autophosporylate, leading to a conformational shift that exposes the binding site for the PKR substrate eIF2α...
December 14, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27965937/hhex-a-crosstalker-between-hcmv-infection-and-proliferation-of-vsmcs
#15
Lingfang Li, Meitong Liu, Leitao Kang, Yifan Li, Ziyu Dai, Bing Wang, Shuiping Liu, Liyu Chen, Yurong Tan, Guojun Wu
Objective: The study was designed to evaluate the role of Human cytomegalovirus (HCMV) infection on homebox (HOX) gene expression and the effects of overexpression of HOX genes on proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Methods: Viral infection was verified by observation of cytopathic effects through inverted microscopy, viral particles by electron microscopy and HCMV IE gene amplification by RT-PCR. cDNA profiling technology was used to screen expression of HOX genes after HCMV infection in VSMCs...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27965404/targeted-genome-editing-in-a-quail-cell-line-using-a-customized-crispr-cas9-system
#16
Jinsoo Ahn, Joonbum Lee, Ju Yeon Park, Keon Bong Oh, Seongsoo Hwang, Chang-Won Lee, Kichoon Lee
Soon after RNA-guided Cas9 (CRISPR-associated protein 9) endonuclease opened a new era of targeted genome editing, the CRISPR/Cas9 platform began to be extensively used to modify genes in various types of cells and organisms. However, successful CRISPR/Cas9-mediated insertion/deletion (indel) mutation remains to be demonstrated in avian cell lines. The objective of this study was to design a poultry-specific CRISPR/Cas9 system to efficiently introduce targeted deletion mutation in chromosomes of the quail muscle clone 7 (QM7) cell line using a customized quail CRISPR vector...
December 13, 2016: Poultry Science
https://www.readbyqxmd.com/read/27956521/dual-targeting-nanoparticles-for-in-vivo-delivery-of-suicide-genes-to-chemotherapy-resistant-ovarian-cancer-cells
#17
Emiliano Cocco, Yang Deng, Erik M Shapiro, Ileana Bortolomai, Salvatore Lopez, Ken Lin, Stefania Bellone, Jiajia Cui, Gulden Menderes, Jonathan D Black, Carlton L Schwab, Elena Bonazzoli, Fan Yang, Federica Predolini, Luca Zammataro, Gary Altwerger, Christopher de Haydu, Mitchell Clark, Julio Alvarenga, Elena Ratner, Masoud Azodi, Dan-Arin Silasi, Peter E Schwartz, Babak Litkouhi, W Mark Saltzman, Alessandro D Santin
Ovarian cancer is the most lethal gynecologic cancer. Claudin-3 and-4, the receptors for Clostridium Perfringens Enterotoxin (CPE), are overexpressed in over 70% of these tumors. Here we synthesized and characterized poly(lactic-co-glycolic-acid) (PLGA) nanoparticles (NP) modified with the carboxi-terminal binding domain of CPE (c-CPE-NP) for the delivery of suicide gene therapy to chemotherapy-resistant ovarian cancer cells. As a therapeutic payload we generated a plasmid encoding for the Diphteria Toxin subunit-A (DT-A) under the transcriptional control of the p16 promoter, a gene highly differentially expressed in ovarian cancer cells...
December 12, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27956170/in-trans-promoter-activation-by-enhancers-in-transient-transfection
#18
N A Smirnov, S B Akopov, D A Didych, L G Nikolaev
Earlier, it was reported that the strong cytomegalovirus enhancer can activate the cytomegalovirus promoter in trans, i.e. as a separate plasmid co-transfected with a promoter-reporter gene construct. Here we demonstrate that the ability of enhancers to activate promoters in trans in transient transfection experiments is a property of not only viral regulatory elements but also of various genomic enhancers and promoters. Enhancer-promoter activation in trans is promoter- and cell type-specific, and accompanied by physical interaction between promoter and enhancer as revealed by chromosome conformation capture assays...
March 1, 2017: Gene
https://www.readbyqxmd.com/read/27935834/viral-dna-sensors-ifi16-and-cyclic-gmp-amp-synthase-possess-distinct-functions-in-regulating-viral-gene-expression-immune-defenses-and-apoptotic-responses-during-herpesvirus-infection
#19
Benjamin A Diner, Krystal K Lum, Jared E Toettcher, Ileana M Cristea
: The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections...
November 15, 2016: MBio
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
#20
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
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