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Vesicular stomatitis virus

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https://www.readbyqxmd.com/read/29148858/from-bench-to-almost-bedside-the-long-road-to-a-licensed-ebola-virus-vaccine
#1
Gary Wong, Emelissa J Mendoza, Francis A Plummer, George F Gao, Gary P Kobinger, Xiangguo Qiu
The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans...
November 17, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29143726/recent-advances-in-vesicular-stomatitis-virus-based-oncolytic-virotherapy-a-5-year-update
#2
Sébastien A Felt, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy is an anti-cancer approach that uses viruses that preferentially infect, replicate in and kill cancer cells. Vesicular stomatitis virus (VSV, a rhabdovirus) is an OV that is currently being tested in the USA in several phase I clinical trials against different malignancies. Several factors make VSV a promising OV: lack of pre-existing human immunity against VSV, a small and easy to manipulate genome, cytoplasmic replication without risk of host cell transformation, independence of cell cycle and rapid growth to high titres in a broad range of cell lines facilitating large-scale virus production...
November 16, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29142134/tnf-mediated-survival-of-cd169-cells-promotes-immune-activation-during-vesicular-stomatitis-virus-infection
#3
Prashant V Shinde, Haifeng C Xu, Sathish Kumar Maney, Andreas Kloetgen, Sukumar Namineni, Yuan Zhuang, Nadine Honke, Namir Shaabani, Nicolas Bellora, Mareike Doerrenberg, Mirko Trilling, Vitaly I Pozdeev, Nico van Rooijen, Stefanie Scheu, Klaus Pfeffer, Paul R Crocker, Masato Tanaka, Sujitha Duggimpudi, Percy Knolle, Mathias Heikenwalder, Jürgen Ruland, Tak W Mak, Dirk Brenner, Aleksandra A Pandyra, Jessica I Hoell, Arndt Borkhardt, Dieter Häussinger, Karl S Lang, Philipp A Lang
Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain unclear. Here we show that tumor necrosis factor is produced by CD11b(+) Ly6C(+)Ly6G(+) cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169(+) cells and in reduced IFN-I production during VSV infection, with a severe disease outcome...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142133/human-adenovirus-infection-causes-the-cellular-mkrn1-e3-ubiquitin-ligase-degradation-involving-the-viral-core-protein-pvii
#4
Raviteja Inturi, Kwangchol Mun, Katrin Singethan, Sabrina Schreiner, Tanel Punga
Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII interacting protein in HAdV-C5-infected cells...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142131/single-dose-trivalent-vesiculovax-vaccine-protects-macaques-from-lethal-ebolavirus-and-marburgvirus-challenge
#5
Demetrius Matassov, Chad E Mire, Theresa Latham, Joan B Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N Agans, Dean J Kobs, Morgan Q S Wendling, Amanda Burnaugh, Thomas L Rudge, Carol L Sabourin, Michael A Egan, David K Clarke, Thomas W Geisbert, John H Eldridge
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142122/adaptive-immune-responses-following-senecavirus-a-infection-in-pigs
#6
Mayara F Maggioli, Steve Lawson, Marcelo de Lima, Lok R Joshi, Tatiane C Faccin, Fernando V Bauermann, Diego G Diel
Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust neutralizing antibody (NA) response, which coincided with and was strongly correlated with VP2- and VP3-specific IgM responses...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29120745/nrp2-and-cd63-are-host-factors-for-lujo-virus-cell-entry
#7
Matthijs Raaben, Lucas T Jae, Andrew S Herbert, Ana I Kuehne, Sarah H Stubbs, Yi-Ying Chou, Vincent A Blomen, Tomas Kirchhausen, John M Dye, Thijn R Brummelkamp, Sean P Whelan
Arenaviruses cause fatal hemorrhagic disease in humans. Old World arenavirus glycoproteins (GPs) mainly engage α-dystroglycan as a cell-surface receptor, while New World arenaviruses hijack transferrin receptor. However, the Lujo virus (LUJV) GP does not cluster with New or Old World arenaviruses. Using a recombinant vesicular stomatitis virus containing LUJV GP as its sole attachment and fusion protein (VSV-LUJV), we demonstrate that infection is independent of known arenavirus receptor genes. A genome-wide haploid genetic screen identified the transmembrane protein neuropilin 2 (NRP2) and tetraspanin CD63 as factors for LUJV GP-mediated infection...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29119400/comparative-study-of-fusogenic-activity-of-h1-and-h5-subtypes-influenza-virus-hemagglutinins
#8
A A Kononova, S V Cheresiz, A V Chechushkov, Yu V Razumova, A G Pokrovskii
Influenza virus hemagglutinins are surface proteins responsible for fusion of the viral and cellular membranes. Their capacity to mediate membrane fusion (fusogenic activity) is studied by various methods, including the syncytium formation and pseudovirus transduction methods. We constructed plasmids coding for genes of three H1 and one H5 hemagglutinins and compared their fusogenic activities. Hemagglutinin capacity to induce syncytium formation did not always correlate with the transduction activity of the respective pseudoviruses...
November 9, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29084253/pivotal-role-for-the-escrt-ii-complex-subunit-eap30-snf8-in-irf3-dependent-innate-antiviral-defense
#9
Kattareeya Kumthip, Darong Yang, Nan L Li, Yunzhi Zhang, Meiyun Fan, Aarti Sethuraman, Kui Li
The activation of interferon (IFN)-regulatory factor-3 (IRF3), characterized by phosphorylation and nuclear translocation of the latent transcription factor, is central to initiating innate antiviral responses. Whereas much has been learned about the upstream pathways and signaling mechanisms leading to IRF3 activation, how activated IRF3 operates in the nucleus to control transcription of IFNs remains obscure. Here we identify EAP30 (a.k.a, SNF8/VPS22), an endosomal sorting complex required for transport (ESCRT)-II subunit, as an essential factor controlling IRF3-dependent antiviral defense...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29076073/dense-granule-protein-7-gra-7-of-toxoplasma-gondii-inhibits-viral-replication-in-vitro-and-in-vivo
#10
Prasanna Weeratunga, Thilina U B Herath, Tae-Hwan Kim, Hyun-Cheol Lee, Jae-Hoon Kim, Byeong-Hoon Lee, Eun-Seo Lee, Kiramage Chathuranga, W A Gayan Chathuranga, Chul-Su Yang, Jin Yeul Ma, Jong-Soo Lee
Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88-dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSV-GFP), influenza A virus (PR8-GFP), coxsackievirus (H3-GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264...
November 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/29072333/large-scale-purification-of-high-purity-%C3%AE-1-antitrypsin-from-cohn-fraction-iv-with-virus-inactivation-by-solvent-detergent-and-dry-heat-treatment
#11
Chaoji Huangfu, Jinchao Zhang, Yuyuan Ma, Junting Jia, Jingxuan Li, Maomin Lv, Xiaowei Ma, Xiong Zhao, Jingang Zhang
α1-antitrypsin (AAT) is widely used to treat patients with congenital AAT deficiency. Cohn Fraction IV (Cohn F IV) is normally discarded during the manufacturing process of albumin but contains approximately 33% of plasma AAT. We established a new process for large-scale purification of AAT from it. LC-ESI-MS/MS and HPLC were applied for qualitative identification and composition analysis, respectively. Stabilizers were optimized for AAT activity protection during lyophilization and dry-heat. Virus inactivation by dry-heat and solvent/detergent (S/D) was validated on a range of viruses...
October 26, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29062886/activating-peripheral-innate-immunity-enables-safe-and-effective-oncolytic-virotherapy-in-the-brain
#12
Lukxmi Balathasan, Vera A Tang, Beta Yadollahi, Jan Brun, Melanie Labelle, Charles Lefebvre, Stephanie L Swift, David F Stojdl
The oncolytic mutant vesicular stomatitis virus VSVΔ51 achieves robust efficacy in multiple extracranial tumor models. Yet for malignancies of the brain, direct intratumoral infusion of VSVΔ51 causes lethal virus-induced neuropathology. Here, we have developed a novel therapeutic regime that uses peripheral immunization with a single sub-lethal dose of VSVΔ51 to establish an acute anti-viral state that enables the safe intracranial (IC) infusion of an otherwise lethal dose of VSVΔ51 within just 6 hr. Although type I interferons alone appeared insufficient to explain this protective phenotype, serum isolated at early time points from primed animals conferred protection against an IC dose of virus...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29034262/detection-of-replication-competent-lentivirus-using-a-qpcr-assay-for-vsv-g
#13
Lindsey M Skrdlant, Randall J Armstrong, Brett M Keidaisch, Mario F Lorente, David L DiGiusto
Lentiviral vectors are a common tool used to introduce new and corrected genes into cell therapy products for treatment of human diseases. Although lentiviral vectors are ideal for delivery and stable integration of genes of interest into the host cell genome, they potentially pose risks to human health, such as integration-mediated transformation and generation of a replication competent lentivirus (RCL) capable of infecting non-target cells. In consideration of the latter risk, all cell-based products modified by lentiviral vectors and intended for patient use must be tested for RCL prior to treatment of the patient...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29020589/phase-2-placebo-controlled-trial-of-two-vaccines-to-prevent-ebola-in-liberia
#14
RANDOMIZED CONTROLLED TRIAL
Stephen B Kennedy, Fatorma Bolay, Mark Kieh, Greg Grandits, Moses Badio, Ripley Ballou, Risa Eckes, Mark Feinberg, Dean Follmann, Birgit Grund, Swati Gupta, Lisa Hensley, Elizabeth Higgs, Krisztina Janosko, Melvin Johnson, Francis Kateh, James Logue, Jonathan Marchand, Thomas Monath, Martha Nason, Tolbert Nyenswah, François Roman, Eric Stavale, Julian Wolfson, James D Neaton, H Clifford Lane
BACKGROUND: The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS: We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated...
October 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29017487/curcumin-is-a-promising-inhibitor-of-genotype-2-porcine-reproductive-and-respiratory-syndrome-virus-infection
#15
Taofeng Du, Yunpeng Shi, Shuqi Xiao, Na Li, Qin Zhao, Angke Zhang, Yuchen Nan, Yang Mu, Yani Sun, Chunyan Wu, Hongtao Zhang, En-Min Zhou
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) could lead to pandemic diseases and huge financial losses to the swine industry worldwide. Curcumin, a natural compound, has been reported to serve as an entry inhibitor of hepatitis C virus, chikungunya virus and vesicular stomatitis virus. In this study, we investigated the potential effect of curcumin on early stages of PRRSV infection. RESULTS: Curcumin inhibited infection of Marc-145 cells and porcine alveolar macrophages (PAMs) by four different genotype 2 PRRSV strains, but had no effect on the levels of major PRRSV receptor proteins on Marc-145 cells and PAMs or on PRRSV binding to Marc-145 cells...
October 10, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28985239/safety-and-immunogenicity-of-rvsv%C3%AE-g-zebov-gp-ebola-vaccine-in-adults-and-children-in-lambar%C3%A3-n%C3%A3-gabon-a-phase-i-randomised-trial
#16
RANDOMIZED CONTROLLED TRIAL
Selidji T Agnandji, José F Fernandes, Emmanuel B Bache, Régis M Obiang Mba, Jessica S Brosnahan, Lumeka Kabwende, Paul Pitzinger, Pieter Staarink, Marguerite Massinga-Loembe, Verena Krähling, Nadine Biedenkopf, Sarah Katharina Fehling, Thomas Strecker, David J Clark, Henry M Staines, Jay W Hooper, Peter Silvera, Vasee Moorthy, Marie-Paule Kieny, Akim A Adegnika, Martin P Grobusch, Stephan Becker, Michael Ramharter, Benjamin Mordmüller, Bertrand Lell, Sanjeev Krishna, Peter G Kremsner
BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. METHODS AND FINDINGS: A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection...
October 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28972551/sophoraflavenone-g-restricts-dengue-and-zika-virus-infection-via-rna-polymerase-interference
#17
Alexandre Sze, David Olagnier, Samar Bel Hadj, Xiaoying Han, Xiao Hong Tian, Hong-Tao Xu, Long Yang, Qingwen Shi, Penghua Wang, Mark A Wainberg, Jian Hui Wu, Rongtuan Lin
Flaviviruses including Zika, Dengue and Hepatitis C virus cause debilitating diseases in humans, and the former are emerging as global health concerns with no antiviral treatments. We investigated Sophora Flavecens, used in Chinese medicine, as a source for antiviral compounds. We isolated Sophoraflavenone G and found that it inhibited Hepatitis C replication, but not Sendai or Vesicular Stomatitis Virus. Pre- and post-infection treatments demonstrated anti-flaviviral activity against Dengue and Zika virus, via viral RNA polymerase inhibition...
October 3, 2017: Viruses
https://www.readbyqxmd.com/read/28954889/herp-binds-tbk1-to-activate-innate-immunity-and-repress-virus-replication-in-response-to-endoplasmic-reticulum-stress
#18
Maolin Ge, Zhen Luo, Zhi Qiao, Yao Zhou, Xin Cheng, Qibin Geng, Yanyan Cai, Pin Wan, Ying Xiong, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
Host innate immunity is crucial for cellular responses against viral infection sensed by distinct pattern recognition receptors and endoplasmic reticulum (ER) stress. Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and neurological diseases. However, the exact mechanism underlying the link between ER stress induced by EV71 infection and host innate immunity is largely unknown. In this study, we demonstrated that EV71 infection induces the homocysteine-induced ER protein (HERP), a modulator of the ER stress response which is dependent on the participation of MAVS...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28931212/temozolomide-resistant-human-brain-tumor-stem-cells-are-susceptible-to-recombinant-vesicular-stomatitis-virus-and-double-deleted-vaccinia-virus-in-vitro
#19
Bin Jiang, Xueqing Lun, Xiaoguang Hao, Yihua Wang, Xin Yin, Dezhang Huang, Wei He, Zhigang Wang
BACKGROUND: Malignant glioma still has a poor prognosis and remains incurable. Although temozolomide (TMZ) has demonstrated antitumor activity, its use recently has been halted because of some patients' resistance to this drug. New treatments are desperately needed. An oncolytic virus (virotherapy) is being developed as a novel cancer therapy. We have previously reported that recombinant Vesicular Stomatitis Virus (VSV-ΔM51) and double deleted Vaccinia Virus (vvDD) infected and killed glioma cell lines in vitro and prolonged survival in animal glioma models...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28918539/accelerating-vaccine-development-during-the-2013-2016-west-african-ebola-virus-disease-outbreak
#20
Elizabeth S Higgs, Sheri A Dubey, Beth A G Coller, Jakub K Simon, Laura Bollinger, Robert A Sorenson, Barthalomew Wilson, Martha C Nason, Lisa E Hensley
The Ebola virus disease outbreak that began in Western Africa in December 2013 was unprecedented in both scope and spread, and the global response was slower and less coherent than was optimal given the scale and pace of the epidemic. Past experience with limited localized outbreaks, lack of licensed medical countermeasures, reluctance by first responders to direct scarce resources to clinical research, community resistance to outside interventions, and lack of local infrastructure were among the factors delaying clinical research during the outbreak...
September 17, 2017: Current Topics in Microbiology and Immunology
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