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https://www.readbyqxmd.com/read/28422714/toll-like-receptor-3-as-an-immunotherapeutic-target-for-kras-mutated-colorectal-cancer
#1
Radhashree Maitra, Titto Augustine, Yitzchak Dayan, Carol Chandy, Matthew Coffey, Sanjay Goel
New therapeutic interventions are essential for improved management of patients with metastatic colorectal cancer (mCRC). This is especially critical for those patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all patients). This patient cohort is excluded from receiving anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical development for patients with chemotherapy refractory KRAS mutated tumors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421365/grass-carp-reovirus-outer-capsid-proteins-vp5-and-vp7-interact-in-vitro
#2
Weisha Liu, Hao Wang, Fei Yu, Liqun Lu
Grass carp reovirus (GCRV) causes viral hemorrhagic disease in cultured grass carp. However, there is no effective means of controlling GCRV. Previous studies have shown, by cryoelectron microscopy, that the outer capsid of GCRV is composed of 200 trimers of VP5-VP7 heterodimers. However, confirmation of this interaction between VP5 and VP7 through molecular biochemistry is still lacking. This study characterized the interactions between VP5 and VP7 in vitro. VP5 was shown to interact with VP7 in a commercial yeast-two-hybrid screen...
April 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28396670/grass-carp-laboratory-of-genetics-and-physiology-2-serves-as-a-negative-regulator-in-retinoic-acid-inducible-gene-i-and-melanoma-differentiation-associated-gene-5-mediated-antiviral-signaling-in-resting-state-and-early-stage-of-grass-carp-reovirus-infection
#3
Youliang Rao, Quanyuan Wan, Chunrong Yang, Jianguo Su
Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)-mediated antiviral responses was identified in Ctenopharyngodon idella kidney cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28389364/cationic-liposome-mediated-delivery-of-reovirus-enhances-the-tumor-cell-killing-efficiencies-of-reovirus-in-reovirus-resistant-tumor-cells
#4
Fuminori Sakurai, Shunsuke Inoue, Tadataka Kaminade, Takuma Hotani, Yuki Katayama, Eri Hosoyamada, Yuichi Terasawa, Masashi Tachibana, Hiroyuki Mizuguchi
Reovirus induces tumor cell death efficiently and specifically, and thus is currently undergoing clinical testing as an anticancer agent. In the intracellular trafficking of reovirus, proteolytic disassembly of reovirus capsid-proteins and subsequent penetration of viral particles into the cytosol are crucial steps. Cathepsins B and L are largely responsible for the proteolytic disassembly of reovirus. Reovirus efficiently lyses tumor cells exhibiting relatively high activities of cathepsins B and L, while tumor cells with low activities of cathepsins B and L are often refractory to reovirus, probably due to inefficient endo/lysosomal escape...
April 4, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28387035/the-frenemies-within-viruses-retrotransposons-and-plasmids-that-naturally-infect-saccharomyces-yeasts
#5
Paul A Rowley
Viruses are a major focus of current research efforts because of their detrimental impact on humanity and their ubiquity within the environment. Bacteriophages have long been used to study host-virus interactions within microbes, but it is often forgotten that the single-celled eukaryote Saccharomyces cerevisiae and related species are infected with double-stranded RNA viruses, single stranded RNA viruses, LTR-retrotransposons and double-stranded DNA plasmids. These intracellular nucleic acid elements have some similarities to higher eukaryotic viruses, i...
April 7, 2017: Yeast
https://www.readbyqxmd.com/read/28386004/reovirus-infection-triggers-inflammatory-responses-to-dietary-antigens-and-development-of-celiac-disease
#6
Romain Bouziat, Reinhard Hinterleitner, Judy J Brown, Jennifer E Stencel-Baerenwald, Mine Ikizler, Toufic Mayassi, Marlies Meisel, Sangman M Kim, Valentina Discepolo, Andrea J Pruijssers, Jordan D Ernest, Jason A Iskarpatyoti, Léa M M Costes, Ian Lawrence, Brad A Palanski, Mukund Varma, Matthew A Zurenski, Solomiia Khomandiak, Nicole McAllister, Pavithra Aravamudhan, Karl W Boehme, Fengling Hu, Janneke N Samsom, Hans-Christian Reinecker, Sonia S Kupfer, Stefano Guandalini, Carol E Semrad, Valérie Abadie, Chaitan Khosla, Luis B Barreiro, Ramnik J Xavier, Aylwin Ng, Terence S Dermody, Bana Jabri
Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28382031/virus-induced-tubules-a-vehicle-for-spread-of-virions-into-ovary-oocyte-cells-of-an-insect-vector
#7
Zhenfeng Liao, Qianzhuo Mao, Jiajia Li, Chengcong Lu, Wei Wu, Hongyan Chen, Qian Chen, Dongsheng Jia, Taiyun Wei
Many arthropod-borne viruses are persistently propagated and transovarially transmitted by female insect vectors through eggs, but the mechanism remains poorly understood. Insect oocytes are surrounded by a layer of follicular cells, which are connected to the oocyte through actin-based microvilli. Here, we demonstrate that a plant reovirus, rice gall dwarf virus (RGDV), exploits virus-containing tubules composed of viral non-structural protein Pns11 to pass through actin-based junctions between follicular cells or through actin-based microvilli from follicular cells into oocyte of its leafhopper vector Recilia dorsalis, thus overcoming transovarial transmission barriers...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28379065/inhibition-of-grass-carp-reovirus-infection-by-dna-aptamers-against-s10-protein
#8
Hongru Liang, Xiaozhe Fu, Lihui Liu, Qiang Lin, Huizhi Guo, Yonggang Li, JiaXu Liu, Zhibin Huang, Ningqiu Li
Grass Carp reovirus (GCRV) is one of the most pathogenic agents among aquareovirus isolates and has the ability to cause a severe epidemic outbreak of hemorrhagic disease, thus resulting in both a high mortality rate during the culture of Grass Carp Ctenopharyngodon idella and an enormous economic loss. Aptamers have been demonstrated to have strong promising applications in antiviral drug development. In the present study, a complementary DNA fragment encoding the S10 gene of GCRV was cloned. The S10 protein was expressed and purified...
June 2017: Journal of Aquatic Animal Health
https://www.readbyqxmd.com/read/28358373/myogenic-differentiation-triggers-pml-nuclear-body-loss-and-daxx-relocalization-to-chromocentres
#9
Jayme Salsman, Lindsy M Rapkin, Nandini N Margam, Roy Duncan, David P Bazett-Jones, Graham Dellaire
The promyelocytic leukemia protein (PML) is expressed in most normal human tissues and forms nuclear bodies (NBs) that have roles in gene regulation and cellular processes such as DNA repair, cell cycle control, and cell fate decisions. Using murine C2C12 myoblasts, we demonstrate that activation of skeletal muscle differentiation results in loss of PML and PML NBs prior to myotube fusion. Myotube formation was associated with marked chromatin reorganization and the relocalization of DAXX from PML NBs to chromocentres...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28326624/current-status-of-clinical-trials-assessing-oncolytic-virus-therapy-for-urological-cancers
#10
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/28322923/microspheres-prime-rmva-boost-vaccination-enhances-humoral-and-cellular-immune-response-in-ifnar-mice-conferring-protection-against-serotypes-1-and-4-of-bluetongue-virus
#11
Alejandro Marín-López, Eva Calvo-Pinilla, Diego Barriales, Gema Lorenzo, Javier Benavente, Alejandro Brun, Jose Manuel Martínez-Costas, Javier Ortego
Bluetongue virus (BTV) is the causative agent of bluetongue disease (BT), which affects domestic and wild ruminants. At the present, 27 different serotypes have been documented. Vaccination has been demonstrated as one of the most effective methods to avoid viral dissemination. To overcome the drawbacks associated with the use of inactivated and attenuated vaccines we engineered a new recombinant BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 that were incorporated into avian reovirus muNS-Mi microspheres (MS-VP2/VP7/NS1) and recombinant modified vaccinia virus Ankara (rMVA)...
March 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28300681/protective-immunity-of-grass-carp-induced-by-dna-vaccine-encoding-capsid-protein-gene-vp7-of-grass-carp-reovirus-using-bacterial-ghost-as-delivery-vehicles
#12
Kai Hao, Xiao-Hui Chen, Xiao-Zhou Qi, Xiao-Bo Yu, En-Qi Du, Fei Ling, Bin Zhu, Gao-Xue Wang
Grass carp reovirus (GCRV) is one of the most pathogenic aquareovirus and can cause lethal hemorrhagic disease in grass carp (Ctenopharyngodon idella). However, management of GCRV infection remains a challenge. Therefore, it is necessary to find effective means for the control of its infection. The uses of bacterial ghost (BG, non-living bacteria) as carriers for DNA delivery have received considerable attentions in veterinary and human vaccines studies. Nevertheless, there is still no report about intramuscular administration of bacterial ghost-based DNA vaccines in fish...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28298603/african-swine-fever-virus-np868r-capping-enzyme-promotes-reovirus-rescue-during-reverse-genetics-by-promoting-reovirus-protein-expression-virion-assembly-and-rna-incorporation-into-infectious-virions
#13
Heather E Eaton, Takeshi Kobayashi, Terence S Dermody, Randal N Johnston, Philippe H Jais, Maya Shmulevitz
Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5' nucleotide of mRNA. Traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme. C3P3, a fusion protein containing T7 RNA polymerase and NP868R, was found to increase protein expression 5 to 10-fold, as compared to T7 RNA polymerase alone, while enhancing reovirus rescue from the current reverse genetics system by 100-fold...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28289863/a-phase-ii-study-of-reolysin-%C3%A2-pelareorep-in-combination-with-carboplatin-and-paclitaxel-for-patients-with-advanced-malignant-melanoma
#14
Devalingam Mahalingam, Christos Fountzilas, Jennifer Moseley, Nicole Noronha, Hue Tran, Romit Chakrabarty, Giovanni Selvaggi, Matthew Coffey, Brad Thompson, John Sarantopoulos
REOLYSIN(®) (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN(®) on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN(®). Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28288679/muscovy-duck-reovirus-%C3%AF-ns-protein-triggers-autophagy-enhancing-virus-replication
#15
Yijian Wu, Longping Cui, Erpeng Zhu, Wuduo Zhou, Quanxi Wang, Xiaoping Wu, Baocheng Wu, Yifan Huang, Hung-Jen Liu
BACKGROUND: Muscovy duck reovirus (MDRV) causes high morbidity and mortality in Muscovy ducklings at 10 days old and can persist in an infected flock until the ducklings of 6 weeks old. It shares common physicochemical properties with avian reovirus (ARV) and differs in coding assignment and pathogenicity. The ARV p17 protein has been shown to trigger autophagy via activation multiple signaling pathways, which benefits virus replication. Since MDRV lacks the p17 protein, whether and how MDRV induces autophagy remains unknown...
March 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28286505/mda5-induces-a-stronger-interferon-response-than-rig-i-to-gcrv-infection-through-a-mechanism-involving-the-phosphorylation-and-dimerization-of-irf3-and-irf7-in-cik-cells
#16
Quanyuan Wan, Chunrong Yang, Youliang Rao, Zhiwei Liao, Jianguo Su
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are critical cytosolic sensors that trigger the production of interferons (IFNs). Though their recognition functions are well identified, their unique roles in the downstream signal transduction remain to be elucidated. Herein, we report the differential effect between grass carp (Ctenopharyngodon idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28279792/transcriptome-data-analysis-of-grass-carp-ctenopharyngodon-idella-infected-by-reovirus-provides-insights-into-two-immune-related-genes
#17
Zao Dai, Jicheng Li, Chengyu Hu, Fang Wang, Binhua Wang, Xiao Shi, Qunhao Hou, Waigen Huang, Gang Lin
Grass carp (Ctenopharyngodon idella) was one of the economically important freshwater fish in China. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in a tremendous loss in the process of grass carp cultivation. Transcriptome analysis could provide a comprehensive understanding of the molecular mechanisms involved in specific biological processes and diseases for the resistance to reovirus infection of grass carp. In this study, the raw data from NCBI (accession number: SRA099702) were analyzed, in which, 50 significant differentially expressed genes by routine transcriptome analysis and 84 notably differentially expressed genes by co-expression network method...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28263320/insect-symbiotic-bacteria-harbour-viral-pathogens-for-transovarial-transmission
#18
Dongsheng Jia, Qianzhuo Mao, Yong Chen, Yuyan Liu, Qian Chen, Wei Wu, Xiaofeng Zhang, Hongyan Chen, Yi Li, Taiyun Wei
Many insects, including mosquitoes, planthoppers, aphids and leafhoppers, are the hosts of bacterial symbionts and the vectors for transmitting viral pathogens(1-3). In general, symbiotic bacteria can indirectly affect viral transmission by enhancing immunity and resistance to viruses in insects(3-5). Whether symbiotic bacteria can directly interact with the virus and mediate its transmission has been unknown. Here, we show that an insect symbiotic bacterium directly harbours a viral pathogen and mediates its transovarial transmission to offspring...
March 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28253857/prediction-of-gcrv-virus-host-protein-interactome-based-on-structural-motif-domain-interactions
#19
Aidi Zhang, Libo He, Yaping Wang
BACKGROUND: Grass carp hemorrhagic disease, caused by grass carp reovirus (GCRV), is the most fatal causative agent in grass carp aquaculture. Protein-protein interactions between virus and host are one avenue through which GCRV can trigger infection and induce disease. Experimental approaches for the detection of host-virus interactome have many inherent limitations, and studies on protein-protein interactions between GCRV and its host remain rare. RESULTS: In this study, based on known motif-domain interaction information, we systematically predicted the GCRV virus-host protein interactome by using motif-domain interaction pair searching strategy...
March 2, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28251973/-exogenous-bacillus-pumilus-rnase-binase-suppresses-the-reproduction-of-reovirus-serotype-1
#20
M A Efimova, R Shah Mahmud, P V Zelenikhin, M I Sabirova, A I Kolpakov, O N Ilinskaya
The experimental study identified the antiviral activity of Bacillus pumilus RNase (binase) against the reovirus of serotype 1/strain Lang. For the first time, it has been found that 50 μg/mL of binase effectively reduced the hemagglutinin and cytocidal activity of reovirus in Vero cell line. The preincubation of the enzyme with reovirus before infection of the cells inhibited the viral replication. To determine the stagedependent effect of reovirus reproduction upon binase inhibition, the infected cells were treated with binase or RNase A at different phases of the infectious cycle...
January 2017: Molekuliarnaia Biologiia
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