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Vesicular stomatitis virus

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https://www.readbyqxmd.com/read/28549145/six-month-safety-data-of-recombinant-vesicular-stomatitis-virus-zaire-ebola-virus-envelope-glycoprotein-vaccine-in-a-phase-3-double-blind-placebo-controlled-randomized-study-in-healthy-adults
#1
Scott A Halperin, Jose R Arribas, Richard Rupp, Charles P Andrews, Laurence Chu, Rituparna Das, Jakub K Simon, Matthew T Onorato, Kenneth Liu, Jason Martin, Frans A Helmond
Background.: This study (NCT02503202) evaluated the safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP). Methods.: Overall, 1197 subjects were randomized 2:2:2:2:1; 1194 were vaccinated with 1 dose of 1 of 3 lots of rVSVΔG- ZEBOV-GP (2 × 107 plaque-forming units [pfu], n = 797; combined-lots group), a single high-dose lot of rVSVΔG-ZEBOV-GP (1 × 108 pfu, n = 264; high-dose group), or placebo (n = 133)...
May 26, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28539437/spontaneous-mutation-at-amino-acid-544-of-the-ebola-glycoprotein-potentiates-virus-entry-and-selection-in-tissue-culture
#2
John B Ruedas, Jason Ladner, Chelsea R Ettinger, Suryaram Gummuluru, Gustavo Palacios, John H Connor
Ebolaviruses have a surface glycoprotein (GP1,2) required for virus attachment and entry into cells. Mutations affecting GP1,2 functions can alter virus growth properties. We generated a recombinant vesicular stomatitis virus encoding Ebola Virus Makona variant GP1,2 (rVSV-MAK-GP) and observed emergence of a T544I mutation in the Makona GP1,2 gene during tissue culture passage in certain cell lines. The T544I mutation emerged within two passages when VSV-MAK-GP was grown on Vero E6, Vero, and BS-C-1 cells but not when it was passaged on Huh7 and HepG2 cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28536351/oncolytic-vesicular-stomatitis-virus-as-a-viro-immunotherapy-defeating-cancer-with-a-hammer-and-anvil
#3
REVIEW
Michael Karl Melzer, Arturo Lopez-Martinez, Jennifer Altomonte
Oncolytic viruses have gained much attention in recent years, due, not only to their ability to selectively replicate in and lyse tumor cells, but to their potential to stimulate antitumor immune responses directed against the tumor. Vesicular stomatitis virus (VSV), a negative-strand RNA virus, is under intense development as an oncolytic virus due to a variety of favorable properties, including its rapid replication kinetics, inherent tumor specificity, and its potential to elicit a broad range of immunomodulatory responses to break immune tolerance in the tumor microenvironment...
February 10, 2017: Biomedicines
https://www.readbyqxmd.com/read/28535668/stability-of-retroviral-vectors-against-ultracentrifugation-is-determined-by-the-viral-internal-core-and-envelope-proteins-used-for-pseudotyping
#4
Soo-Hyun Kim, Kwang-Il Lim
Retroviral and lentiviral vectors are mostly pseudotyped and often purified and concentrated via ultracentrifugation. In this study, we quantified and compared the stabilities of retroviral [murine leukemia virus (MLV)-based] and lentiviral [human immunodeficiency virus (HIV)-1-based] vectors pseudotyped with relatively mechanically stable envelope proteins, vesicular stomatitis virus glycoproteins (VSVGs), and the influenza virus WSN strain envelope proteins against ultracentrifugation. Lentiviral genomic and functional particles were more stable than the corresponding retroviral particles against ultracentrifugation when pseudotyped with VSVGs...
May 2, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28530650/multi-virion-infectious-units-arise-from-free-viral-particles-in-an-enveloped-virus
#5
José M Cuevas, María Durán-Moreno, Rafael Sanjuán
Many animal viruses are enveloped in a lipid bilayer taken up from cellular membranes. Because viral surface proteins bind to these membranes to initiate infection, we hypothesized that free virions may also be capable of interacting with the envelopes of other virions extracellularly. Here, we demonstrate this hypothesis in the vesicular stomatitis virus (VSV), a prototypic negative-strand RNA virus composed of an internal ribonucleocapsid, a matrix protein and an external envelope(1). Using microscopy, dynamic light scattering, differential centrifugation and flow cytometry, we show that free viral particles can spontaneously aggregate into multi-virion infectious units...
May 22, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#6
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28516287/spread-of-poxviruses-in-livestock-in-brazil-associated-with-cases-of-double-and-triple-infection
#7
Mateus Laguardia-Nascimento, Ana Paula Ferreira de Oliveira, Isabela Ciarlini Azevedo, Anselmo Vasconcelos Rivetti Júnior, Marcelo Fernandes Camargos, Antônio Augusto Fonseca Júnior
The objective of this work is to describe the distribution of outbreaks of vaccinia virus (VACV), pseudocowpox virus (PCPV), and bovine papular stomatitis virus (BSPV) in Brazil. The Official Laboratory of the Brazilian Ministry of Agriculture received 89 samples from different locations in Brazil in 2015 and 2016 for diagnosis of vesicular and exanthematous disease. Poxvirus coinfections occurred in 11 out of 33 outbreaks, including the first reported triple infection by BPSV, PCPV, and VACV. This occurrence may be associated with the circulation of these viruses in Brazilian cattle...
May 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28514874/oncolytic-recombinant-vesicular-stomatitis-virus-vsv-is-nonpathogenic-and-non-transmissible-in-pigs-a-natural-host-of-vsv
#8
Lauro Velazquez-Salinas, Shruthi Naik, Steven Pauszek, Kah-Whye Peng, Stephen J Russell, Luis Rodriguez
Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally causes disease in livestock including horses, cattle and pigs. The two main identified VSV strains are the New Jersey (VSNJV) and Indiana (VSIV) strains. VSV is a rapidly replicating, potently immunogenic virus that has been engineered to develop novel oncolytic therapies for cancer treatment. Swine are a natural host for VSV and provide a relevant and well-established model, amenable to biological sampling to monitor virus shedding and neutralizing antibodies...
May 17, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28487016/the-expression-level-of-c19mc-mirnas-in-early-pregnancy-and-in-response-to-viral-infection
#9
Tina M F Dumont, Jean-Francois Mouillet, Avaraham Bayer, Christina L Gardner, William B Klimstra, Dana G Wolf, Simcha Yagel, Fabiola Balmir, Anna Binstock, Joseph S Sanfilippo, Carolyn B Coyne, Jacob C Larkin, Yoel Sadovsky
INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR...
May 2017: Placenta
https://www.readbyqxmd.com/read/28478671/autonomous-cell-migration-to-csf1-sources-via-a-synthetic-protein-based-system
#10
Anam Qudrat, Kevin Truong
Inflammatory lesions, often seen in diseases such as rheumatoid arthritis, atherosclerosis and cancer, feature an acidic (i.e., low pH) microenvironment rampant with cytokines, such as CSF1. For potential therapeutic intervention targeted at these CSF1 sources, we have assembled a system of four proteins inside a cell (i.e., HEK293) that initially had no natural CSF1-seeking ability. This system included a newly engineered CSF1 chimera receptor (named CSF1Rchi), the previously engineered Ca(2+) activated RhoA (i...
May 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28464285/elimination-of-gpr146-mediated-antiviral-function-through-irf3-hes1-signaling-pathway
#11
Hongjun Huang, Na Zhang, Qingqing Xiong, Ruoyu Chen, Chengfei Zhang, Ning Wang, Li Wang, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most important host defense against viral infection, interferon (IFN) stimulates hundreds of antiviral genes (ISGs) that together establish an "antiviral state". However, the antiviral function of most ISGs in viral infection still need further exploration. Here, we demonstrated that the expression of G-protein-coupled receptor 146 (GPR146) is highly increased by both IFN-β and IFN-γ in a STAT1-dependent signaling pathway. Most importantly, overexpression of GPR146 protects the host cells from Vesicular stomatitis virus and Newcastle disease virus infection but not Herpes simplex virus...
May 2, 2017: Immunology
https://www.readbyqxmd.com/read/28458537/pseudotyping-exosomes-for-enhanced-protein-delivery-in-mammalian-cells
#12
Conary Meyer, Joseph Losacco, Zachary Stickney, Lingxuan Li, Gerard Marriott, Biao Lu
Exosomes are cell-derived nanovesicles that hold promise as living vehicles for intracellular delivery of therapeutics to mammalian cells. This potential, however, is undermined by the lack of effective methods to load exosomes with therapeutic proteins and to facilitate their uptake by target cells. Here, we demonstrate how a vesicular stomatitis virus glycoprotein (VSVG) can both load protein cargo onto exosomes and increase their delivery ability via a pseudotyping mechanism. By fusing a set of fluorescent and luminescent reporters with VSVG, we show the successful targeting and incorporation of VSVG fusions into exosomes by gene transfection and fluorescence tracking...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28434944/dose-dependent-t-cell-dynamics-and-cytokine-cascade-following-rvsv-zebov-immunization
#13
Christine Dahlke, Rahel Kasonta, Sebastian Lunemann, Verena Krähling, Madeleine E Zinser, Nadine Biedenkopf, Sarah K Fehling, My L Ly, Anne Rechtien, Hans C Stubbe, Flaminia Olearo, Saskia Borregaard, Alen Jambrecina, Felix Stahl, Thomas Strecker, Markus Eickmann, Marc Lütgehetmann, Michael Spohn, Stefan Schmiedel, Ansgar W Lohse, Stephan Becker, Marylyn M Addo
BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date...
April 5, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28433889/quantitative-proteomic-profiling-for-clarification-of-the-crucial-roles-of-lysosomes-in-microbial-infections
#14
Benhong Xu, Yanpan Gao, Shaohua Zhan, Wei Ge
Lysosomes play vital roles in both innate and adaptive immunity. It is widely accepted that lysosomes do not function exclusively as a digestive organelle. It is also involved in the process of immune cells against pathogens. However, the changes in the lysosomal proteome caused by infection with various microbes are still largely unknown, and our understanding of the proteome of the purified lysosome is another obstacle that needs to be resolved. Here, we performed a proteomic study on lysosomes enriched from THP1 cells after infection with Listeria monocytogenes (L...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28427845/development-of-a-micro-neutralization-assay-for-ebolaviruses-using-a-replication-competent-vesicular-stomatitis-hybrid-virus-and-a-quantitative-pcr-readout
#15
Stella S Lee, Kathryn Phy, Keith Peden, Li Sheng-Fowler
Development of vaccines against highly pathogenic viruses that could also be used as agents of bioterrorism is both a public health issue and a national security priority. Methods that can quantify neutralizing antibodies will likely be crucial in demonstrating vaccine effectiveness, as most licensed viral vaccines are effective due to their capacity to elicit neutralizing antibodies. Assays to determine whether antibodies are neutralizing traditionally involve infectious virus, and the assay most commonly used is the plaque-reduction neutralization test (PRNT)...
April 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28416650/epigenetic-regulator-cxxc5-recruits-dna-demethylase-tet2-to-regulate-tlr7-9-elicited-ifn-response-in-pdcs
#16
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28404856/a-dose-dependent-plasma-signature-of-the-safety-and-immunogenicity-of-the-rvsv-ebola-vaccine-in-europe-and-africa
#17
Angela Huttner, Christophe Combescure, Stéphane Grillet, Mariëlle C Haks, Edwin Quinten, Christine Modoux, Selidji Todagbe Agnandji, Jessica Brosnahan, Julie-Anne Dayer, Ali M Harandi, Laurent Kaiser, Donata Medaglini, Tom Monath, Pascale Roux-Lombard, Peter G Kremsner, Tom H M Ottenhoff, Claire-Anne Siegrist
The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404855/genome-wide-screening-uncovers-the-significance-of-n-sulfation-of-heparan-sulfate-as-a-host-cell-factor-for-chikungunya-virus-infection
#18
Atsushi Tanaka, Uranan Tumkosit, Shota Nakamura, Daisuke Motooka, Natsuko Kishishita, Thongkoon Priengprom, Areerat Sa-Ngasang, Taroh Kinoshita, Naokazu Takeda, Yusuke Maeda
The molecular mechanisms underlying chikungunya virus (CHIKV) infection are poorly characterized. In this study, we analyzed the host factors involved in CHIKV infection using genome-wide screening. Human haploid HAP1 cells, into which an exon-trapping vector was introduced, were challenged with a vesicular stomatitis virus pseudotype bearing the CHIKV E3-E1 envelope proteins. Analysis of genes enriched in the cells resistant to the pseudotyped virus infection unveiled a critical role of N-sulfation of heparan sulfate (HS) for the infectivity of a clinically isolated CHIKV Thai #16856 strain to HAP1 cells...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28396572/vesicular-stomatitis-virus-n-protein-specific-single-domain-antibody-fragments-inhibit-replication
#19
Leo Hanke, Florian I Schmidt, Kevin E Knockenhauer, Benjamin Morin, Sean Pj Whelan, Thomas U Schwartz, Hidde L Ploegh
The transcription and replication machinery of negative-stranded RNA viruses presents a possible target for interference in the viral life cycle. We demonstrate the validity of this concept through the use of cytosolically expressed single-domain antibody fragments (VHHs) that protect cells from a lytic infection with vesicular stomatitis virus (VSV) by targeting the viral nucleoprotein N. We define the binding sites for two such VHHs, 1004 and 1307, by X-ray crystallography to better understand their inhibitory properties...
April 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28392573/inducible-rubicon-facilitates-viral-replication-by-antagonizing-interferon-production
#20
Yushun Wan, Wei Cao, Tao Han, Sheng Ren, Jian Feng, TieLong Chen, Jun Wang, Ruth Broering, Mengji Lu, Ying Zhu
The RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon) protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner, but little is known regarding the role of Rubicon during viral infection. Here, we performed functional studies of the identified target in interferon (IFN) signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN. The Rubicon protein levels were elevated in peripheral blood mononuclear cells, sera and liver tissues from patients with hepatitis B virus (HBV) infection relative to those in healthy individuals...
April 10, 2017: Cellular & Molecular Immunology
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