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https://www.readbyqxmd.com/read/28326624/current-status-of-clinical-trials-assessing-oncolytic-virus-therapy-for-urological-cancers
#1
REVIEW
Satoru Taguchi, Hiroshi Fukuhara, Yukio Homma, Tomoki Todo
Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEX(GM)(-)(CSF) ), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials...
March 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28295920/importin-%C3%AE-1-targeting-by-hepatitis-c-virus-ns3-4a-protein-restricts-irf3-and-nf-%C3%AE%C2%BAb-signaling-of-ifnb1-antiviral-response
#2
Bridget Gagné, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection...
March 13, 2017: Traffic
https://www.readbyqxmd.com/read/28295247/targeting-c3a-c5a-receptors-inhibits-human-mesangial-cell-proliferation-and-alleviates-iga-nephropathy-in-mice
#3
Ying Zhang, Xianli Yan, Ting Zhao, Qihe Xu, Qi Peng, Ruimin Hu, Songxia Quan, Yali Zhou, Guolan Xing
Complement activation has a deep pathogenic influence in IgA nephropathy (IgAN). C3a and C5a, small cleavage fragments generated by complement activation, are key mediators of inflammation. The fragments exert broad pro-inflammatory effects by binding to specific receptors (C3aR and C5aR, respectively). However, no studies thus far have investigated the effects of C3a, C5a and their receptors on IgAN. We observed that C3aR and C5aR antagonists repressed IgA-induced cell proliferation and IL-6 and MCP-1 production in cultured human mesangial cells (HMCs)...
March 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28273895/the-dynamic-interacting-landscape-of-mapl-reveals-essential-functions-for-sumoylation-in-innate-immunity
#4
Karine Doiron, Vanessa Goyon, Etienne Coyaud, Sanjeeva Rajapakse, Brian Raught, Heidi M McBride
Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264968/tim-3-is-a-marker-of-plasmacytoid-dendritic-cell-dysfunction-during-hiv-infection-and-is-associated-with-the-recruitment-of-irf7-and-p85-into-lysosomes-and-with-the-submembrane-displacement-of-tlr9
#5
Jordan Ari Schwartz, Kiera L Clayton, Shariq Mujib, Hongliang Zhang, A K M Nur-Ur Rahman, Jun Liu, Feng Yun Yue, Erika Benko, Colin Kovacs, Mario A Ostrowski
In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28262547/a-role-for-klf4-in-promoting-the-metabolic-shift-via-tcl1-during-induced-pluripotent-stem-cell-generation
#6
Ken Nishimura, Shiho Aizawa, Fransiska Liliani Nugroho, Emi Shiomitsu, Yen Thi Hai Tran, Phuong Linh Bui, Evgeniia Borisova, Yuta Sakuragi, Hitomi Takada, Akira Kurisaki, Yohei Hayashi, Aya Fukuda, Mahito Nakanishi, Koji Hisatake
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is accompanied by morphological, functional, and metabolic alterations before acquisition of full pluripotency. Although the genome-wide effects of the reprogramming factors on gene expression are well documented, precise mechanisms by which gene expression changes evoke phenotypic responses remain to be determined. We used a Sendai virus-based system that permits reprogramming to progress in a strictly KLF4-dependent manner to screen for KLF4 target genes that are critical for the progression of reprogramming...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28251971/-biomarkers-of-prostate-cancer-sensitivity-to-the-sendai-virus
#7
A A Belova, A O Sosnovtseva, A V Lipatova, K M Njushko, N N Volchenko, M M Belyakov, O V Sudalenko, A A Krasheninnikov, P V Shegai, A F Sadritdinova, M S Fedorova, N V Vorobjov, B Y Alekseev, A D Kaprin, A V Kudryavtseva
Metastatic prostate cancer is often associated with either primary or intractable castration-resistant prostate cancer (CRPC), thus justifying the search for entirely new ways of treatment. Oncolytic viruses are able to selectively induce the death of tumor cells without affecting normal cells. A murine Sendai virus has potential to be used as an oncolytic agent. However, tumors vary in their sensitivity to different viruses, prompting us to attempt to identify corresponding biomarkers that reflect the interaction of cancer cells and the virus...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28250126/respiratory-syncytial-virus-rsv-vaccine-vectored-by-a-stable-chimeric-and-replication-deficient-sendai-virus-protects-mice-without-inducing-enhanced-disease
#8
Marian Alexander Wiegand, Gianni Gori-Savellini, Claudia Gandolfo, Guido Papa, Christine Kaufmann, Eva Felder, Alessandro Ginori, Maria Giulia Disanto, Donatella Spina, Maria Grazia Cusi
Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known as a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. Exchanging the ectodomain of the SeV F protein with its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28159912/identification-of-tbk1-complexes-required-for-the-phosphorylation-of-irf3-and-the-production-of-interferon-b
#9
Siddharth Bakshi, Jordan Taylor, Sam Strickson, Thomas Macartney, Philip Cohen
The double-stranded RNA mimetic poly(I:C) and LPS activate Toll-like Receptor 3 (TLR3) and TLR4, respectively, triggering the activation of TANK-Binding Kinase 1 (TBK1) complexes, the phosphorylation of Interferon Regulatory Factor 3 (IRF3) and transcription of the Interferon b (IFNb) gene. Here, we demonstrate that the TANK-TBK1 and Optineurin (OPTN)-TBK1 complexes control this pathway. The poly(I:C)- or LPS-stimulated phosphorylation of IRF3 at Ser396 and production of IFNb were greatly reduced in bone-marrow-derived macrophages (BMDM) from TANK knock-out (KO) mice crossed to knock-in mice-expressing the ubiquitin-binding-defective OPTN[D477N] mutant...
February 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28148787/sars-coronavirus-nucleocapsid-inhibits-type-i-interferon-production-by-interfering-with-trim25-mediated-rig-i-ubiquitination
#10
Yong Hu, Wei Li, Ting Gao, Yan Cui, Yanwen Jin, Ping Li, Qingjun Ma, Xuan Liu, Cheng Cao
Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a coronavirus (SARS-CoV) that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28129782/cord-blood-cell-derived-ipscs-as-a-new-candidate-for-chondrogenic-differentiation-and-cartilage-regeneration
#11
Yoojun Nam, Yeri Alice Rim, Seung Min Jung, Ji Hyeon Ju
BACKGROUND: The native articular cartilage lacks the ability to heal. Currently, ex vivo expanded chondrocytes or bone marrow-derived mesenchymal stem cells are used to regenerate the damaged cartilage. With unlimited self-renewal ability and multipotency, human induced pluripotent stem cells (hiPSCs) have been highlighted as a new replacement cell source for cartilage repair. Still, further research is needed on cartilage regeneration using cord blood mononuclear cell-derived hiPSCs (CBMC-hiPSCs)...
January 28, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28129374/il-27-limits-type-2-immunopathology-following-parainfluenza-virus-infection
#12
Gaia Muallem, Sagie Wagage, Yan Sun, Jonathan H DeLong, Alex Valenzuela, David A Christian, Gretchen Harms Pritchard, Qun Fang, Elizabeth L Buza, Deepika Jain, M Merle Elloso, Carolina B López, Christopher A Hunter
Respiratory paramyxoviruses are important causes of morbidity and mortality, particularly of infants and the elderly. In humans, a T helper (Th)2-biased immune response to these infections is associated with increased disease severity; however, little is known about the endogenous regulators of these responses that may be manipulated to ameliorate pathology. IL-27, a cytokine that regulates Th2 responses, is produced in the lungs during parainfluenza infection, but its role in disease pathogenesis is unknown...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28125002/feline-panleucopenia-virus-ns2-suppresses-the-host-ifn-%C3%AE-induction-by-disrupting-the-interaction-between-tbk1-and-sting
#13
Hongtao Kang, Dafei Liu, Jin Tian, Xiaoliang Hu, Xiaozhan Zhang, Hang Yin, Hongxia Wu, Chunguo Liu, Dongchun Guo, Zhijie Li, Qian Jiang, Jiasen Liu, Liandong Qu
Feline panleucopenia virus (FPV) is a highly infectious pathogen that causes severe diseases in pets, economically important animals and wildlife in China. Although FPV was identified several years ago, little is known about how it overcomes the host innate immunity. In the present study, we demonstrated that infection with the FPV strain Philips-Roxane failed to activate the interferon β (IFN-β) pathway but could antagonize the induction of IFN stimulated by Sendai virus (SeV) in F81 cells. Subsequently, by screening FPV nonstructural and structural proteins, we found that only nonstructural protein 2 (NS2) significantly suppressed IFN expression...
January 23, 2017: Viruses
https://www.readbyqxmd.com/read/28117800/generation-of-integration-free-induced-pluripotent-stem-cells-from-human-peripheral-blood-mononuclear-cells-using-episomal-vectors
#14
Wei Wen, Jian-Ping Zhang, Wanqiu Chen, Cameron Arakaki, Xiaolan Li, David Baylink, Gary D Botimer, Jing Xu, Weiping Yuan, Tao Cheng, Xiao-Bing Zhang
Induced Pluripotent Stem Cells (iPSCs) hold great promise for disease modeling and regenerative therapies. We previously reported the use of Episomal Vectors (EV) to generate integration-free iPSCs from peripheral blood mononuclear cells (PB MNCs). The episomal vectors used are DNA plasmids incorporated with oriP and EBNA1 elements from the Epstein-Barr (EB) virus, which allow for replication and long-term retainment of plasmids in mammalian cells, respectively. With further optimization, thousands of iPSC colonies can be obtained from 1 mL of peripheral blood...
January 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28117672/reprogramming-methods-do-not-affect-gene-expression-profile-of-human-induced-pluripotent-stem-cells
#15
Marta Trevisan, Giovanna Desole, Giulia Costanzi, Enrico Lavezzo, Giorgio Palù, Luisa Barzon
Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts...
January 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28115528/human-dendritic-cell-derived-induced-pluripotent-stem-cell-lines-are-not-immunogenic
#16
Arvind Chhabra, I-Ping Chen, Deepika Batra
Donor-specific induced pluripotent stem cells (iPSC) can be used to generate desired cell types, including naive immune effectors, for the treatment of different diseases. However, a greater understanding of the inherent immunogenicity of human iPSC and their cellular derivatives is needed for the development of safe and effective cell-replacement therapies, given that studies in mouse models claimed that the syngenic mouse iPSC lines can be immunogenic. We report the characterization of the innate and adaptive immune mechanisms in human iPSC lines derived from peripheral blood-derived dendritic cells using a nonintegrating RNA virus, Sendai virus...
January 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28077588/first-in-human-evaluation-of-the-safety-and-immunogenicity-of-an-intranasally-administered-replication-competent-sendai-virus-vectored-hiv-type-1-gag-vaccine-induction-of-potent-t-cell-or-antibody-responses-in-prime-boost-regimens
#17
Julien Nyombayire, Omu Anzala, Brian Gazzard, Etienne Karita, Philip Bergin, Peter Hayes, Jakub Kopycinski, Gloria Omosa-Manyonyi, Akil Jackson, Jean Bizimana, Bashir Farah, Eddy Sayeed, Christopher L Parks, Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Len Dally, Burc Barin, Harriet Park, Jill Gilmour, Angela Lombardo, Jean-Louis Excler, Patricia Fast, Dagna S Laufer, Josephine H Cox
BACKGROUND:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. METHODS:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28067018/global-quantitative-proteomic-analysis-profiles-host-protein-expression-in-response-to-sendai-virus-infection
#18
Sheng-Lin Zhu, Xi Chen, Liang-Jie Wang, Wei-Wei Wan, Qi-Lin Xin, Wei Wang, Gengfu Xiao, Lei-Ke Zhang
Sendai virus is an enveloped non-segmented negative-strand RNA virus that belongs to the genus Respirovirus of the Paramyxoviridae family. As a model pathogen, SeV has been extensively studied to define the basic biochemical and molecular biologic properties of the paramyxoviruses. In addition, SeV-infected host cells were widely employed to uncover the mechanism of innate immune response. To identify proteins involved in the SeV infection process or the SeV-induced innate immune response process, system-wide evaluations of SeV-host interactions have been performed...
January 9, 2017: Proteomics
https://www.readbyqxmd.com/read/28060376/induction-of-necroptotic-cell-death-by-viral-activation-of-the-rig-i-or-sting-pathway
#19
Suruchi N Schock, Neha V Chandra, Yuefang Sun, Takashi Irie, Yoshinori Kitagawa, Bin Gotoh, Laurent Coscoy, Astar Winoto
Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. To see how general the interplay between viruses and necroptosis is, we surveyed seven different viruses...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060310/induced-pluripotent-stem-cell-generation-from-blood-cells-using-sendai-virus-and-centrifugation
#20
Yeri Alice Rim, Yoojun Nam, Ji Hyeon Ju
The recent development of human induced pluripotent stem cells (hiPSCs) proved that mature somatic cells can return to an undifferentiated, pluripotent state. Now, reprogramming is done with various types of adult somatic cells: keratinocytes, urine cells, fibroblasts, etc. Early experiments were usually done with dermal fibroblasts. However, this required an invasive surgical procedure to obtain fibroblasts from the patients. Therefore, suspension cells, such as blood and urine cells, were considered ideal for reprogramming because of the convenience of obtaining the primary cells...
December 21, 2016: Journal of Visualized Experiments: JoVE
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