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Vesicular stomatitis virus

Jovan Nikolic, Laura Belot, Hélène Raux, Pierre Legrand, Yves Gaudin, Aurélie A Albertini
Vesicular stomatitis virus (VSV) is an oncolytic rhabdovirus and its glycoprotein G is widely used to pseudotype other viruses for gene therapy. Low-density lipoprotein receptor (LDL-R) serves as a major entry receptor for VSV. Here we report two crystal structures of VSV G in complex with two distinct cysteine-rich domains (CR2 and CR3) of LDL-R, showing that their binding sites on G are identical. We identify two basic residues on G, which are essential for its interaction with CR2 and CR3. Mutating these residues abolishes VSV infectivity even though VSV can use alternative receptors, indicating that all VSV receptors are members of the LDL-R family...
March 12, 2018: Nature Communications
Guanghui Qian, Xiaohan Hu, Gen Li, Yueyue Ding, Liyan Zhu, Hui Zheng, Mei Li, Zhiheng Li, Jian Pan, Yiping Li, Gang Li, Chun Yang, Ying Liu, Yi Xie, Haitao Lv
Protein ubiquitination and deubiquitination enzymes are widely involved in innate immune responses. The ubiquitin specific protease 25 (USP25), a deubiquitinating enzyme, has been demonstrated to play an important role in virus infection and immunity. However, how USP25 is degraded and regulated by E3 ubiquitin ligases remains poorly understood. Here, we identified Smad ubiquitin regulatory factor 1(Smurf1) as a first novel E3 ubiquitin ligase of USP25. Smurf1 overexpression decreases USP25 protein turnover, and the E3 ligase enzymatic activity of Smurf1 is required for USP25 degradation...
March 5, 2018: Biochemical and Biophysical Research Communications
Janine Kimpel, Carles Urbiola, Iris Koske, Reinhard Tober, Zoltan Banki, Guido Wollmann, Dorothee von Laer
Previously, we described VSV-GP, a modified version of the vesicular stomatitis virus, as a non-neurotoxic oncolytic virus that is effective for the treatment of malignant glioblastoma and ovarian cancer. Here, we evaluate the therapeutic efficacy of VSV-GP for malignant melanoma. All of the human, mouse, and canine melanoma cell lines that were tested, alongside most primary human melanoma cultures, were infected by VSV-GP and efficiently killed. Additionally, we found that VSV-GP prolonged the survival of mice in both a xenograft and a syngeneic mouse model...
March 2, 2018: Viruses
U Gravemann, W Handke, C Sumian, I Alvarez, S Reichenberg, T H Müller, A Seltsam
BACKGROUND: Photodynamic treatment using methylene blue (MB) and visible light is in routine use for pathogen inactivation of human plasma in different countries. Ambient and product temperature conditions for human plasma during production may vary between production sites. The influence of different temperature conditions on virus inactivation capacity and plasma quality of the THERAFLEX MB-Plasma procedure was investigated in this study. METHODS: Plasma units equilibrated to 5 ± 2°C, room temperature (22 ± 2°C) or 30 ± 2°C were treated with MB/light and comparatively assessed for the inactivation capacity for three different viruses, concentrations of MB and its photoproducts, activity of various plasma coagulation factors and clotting time...
February 27, 2018: Vox Sanguinis
Suman Bishnoi, Ritudhwaj Tiwari, Sharad Gupta, Siddappa N Byrareddy, Debasis Nayak
Modern oncotherapy approaches are based on inducing controlled apoptosis in tumor cells. Although a number of apoptosis-induction approaches are available, site-specific delivery of therapeutic agents still remain the biggest hurdle in achieving the desired cancer treatment benefit. Additionally, systemic treatment-induced toxicity remains a major limiting factor in chemotherapy. To specifically address drug-accessibility and chemotherapy side effects, oncolytic virotherapy (OV) has emerged as a novel cancer treatment alternative...
February 23, 2018: Viruses
Lauro Velazquez-Salinas, Steven J Pauszek, Antonio Verdugo-Rodriguez, Luis L Rodriguez
We report here the complete genome sequences of two vesicular stomatitis New Jersey virus (VSNJV) field strains isolated from epithelial lesions from naturally infected animals in Mexico and the United States. The close phylogenetic relationship of these isolates makes them an ideal model for assessing potential genetic factors linked with the emergence of VSNJV in the United States.
February 15, 2018: Genome Announcements
Kate M Franz, William J Neidermyer, Yee-Joo Tan, Sean P J Whelan, Jonathan C Kagan
In mammalian cells, IFN responses that occur during RNA and DNA virus infections are activated by distinct signaling pathways. The RIG-I-like-receptors (RLRs) bind viral RNA and engage the adaptor MAVS (mitochondrial antiviral signaling) to promote IFN expression, whereas cGAS (cGMP-AMP synthase) binds viral DNA and activates an analogous pathway via the protein STING (stimulator of IFN genes). In this study, we confirm that STING is not necessary to induce IFN expression during RNA virus infection but also find that STING is required to restrict the replication of diverse RNA viruses...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ryan H Gumpper, Weike Li, Carlos H Castañeda, M José Scuderi, James K Bashkin, Ming Luo
Polyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the structured RNA bound in the nucleocapsid of a negative strand RNA virus. Vesicular stomatitis virus (VSV) was selected as a prototype virus to test this possibility since its genomic RNA encaspsidated in the nucleocapsid forms a structure resembling one strand of an A-form RNA duplex...
February 7, 2018: Journal of Virology
Francesca Torelli, Steffen Zander, Heinz Ellerbrok, Georg Kochs, Rainer G Ulrich, Christian Klotz, Frank Seeber
Rodent species like Myodes glareolus and Microtus spp. are natural reservoirs for many zoonotic pathogens causing human diseases and are gaining increasing interest in the field of eco-immunology as candidate animal models. Despite their importance the lack of immunological reagents has hampered research in these animal species. Here we report the recombinant production and functional characterization of IFN-γ, a central mediator of host's innate and adaptive immune responses, from the bank vole M. glareolus...
February 12, 2018: Scientific Reports
Irina A Tarasova, Alesya V Tereshkova, Anna A Lobas, Elizaveta M Solovyeva, Alena S Sidorenko, Vladimir Gorshkov, Frank Kjeldsen, Julia A Bubis, Mark V Ivanov, Irina Y Ilina, Sergei A Moshkovskii, Peter M Chumakov, Mikhail V Gorshkov
An acquisition of increased sensitivity of cancer cells to viruses is a common outcome of malignant progression that justifies the development of oncolytic viruses as anticancer therapeutics. Studying molecular changes that underlie the sensitivity to viruses would help to identify cases where oncolytic virus therapy would be most effective. We quantified changes in protein abundances in two glioblastoma multiforme (GBM) cell lines that differ in the ability to induce resistance to vesicular stomatitis virus (VSV) infection in response to type I interferon (IFN) treatment...
January 5, 2018: Oncotarget
Tiphaine Delaunay, Mathilde Violland, Nicolas Boisgerault, Soizic Dutoit, Virginie Vignard, Christian Münz, Monique Gannage, Brigitte Dréno, Kristine Vaivode, Dace Pjanova, Nathalie Labarrière, Yaohe Wang, E Antonio Chiocca, Fabrice Le Boeuf, John C Bell, Philippe Erbs, Frédéric Tangy, Marc Grégoire, Jean-François Fonteneau
Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1...
2018: Oncoimmunology
Joshua D Frenster, Julio Inocencio, Dimitris G Placantonakis
This chapter provides detailed step-by-step instructions for the production of lentiviral particles and the transduction of primary human glioblastoma cultures. Lentiviruses stably transduce both dividing and non-dividing cells, such as quiescent cancer stem cell populations. The viral envelope is pseudotyped with the vesicular stomatitis virus envelope glycoprotein G (VSV-G), which renders the lentiviral particles pantropic, so that they can infect theoretically all cell types. The third generation packaging system used in this protocol produces lentiviruses with important safety features, including replication incompetence and self-inactivation (SIN)...
2018: Methods in Molecular Biology
Krishnamurthy Konduru, Amy C Shurtleff, Sina Bavari, Gerardo Kaplan
Ebola virus (EBOV), classified as a category A agent by the CDC and NIH, requires BSL-4 containment and induces high morbidity and mortality in humans. The 2013-2015 epidemic in West Africa underscored the urgent need to develop vaccines and therapeutics to prevent and treat EBOV disease. Neutralization assays are needed to evaluate the efficacy of EBOV vaccines and antibody therapies. Pseudotyped viruses based on nonpathogenic or attenuated vectors reduce the risks involved in the evaluation of neutralizing antibodies against highly pathogenic viruses...
January 16, 2018: Journal of Virological Methods
Laura Marcos-Villar, Juan Díaz-Colunga, Juan Sandoval, Noelia Zamarreño, Sara Landeras-Bueno, Manel Esteller, Ana Falcón, Amelia Nieto
Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection...
January 19, 2018: Scientific Reports
Tomasz Tomczyk, Grażyna Wróbel, Radosław Chaber, Iwona Siemieniec, Egbert Piasecki, Małgorzata Krzystek-Korpacka, Beata U Orzechowska
BACKGROUND: Oncolytic vesicular stomatitis virus (VSV) can be delivered intravenously to target primary and metastatic lesions, but the interaction between human peripheral blood leukocytes (PBLs) and VSV remains poorly understood. Our study aimed to assess the overall immunological consequences of ex vivo infection of PBLs with VSV. METHODS: Phenotypic analysis of lymphocyte subsets and apoptosis were evaluated with flow cytometry. Caspase 3/7 activity was detected by luminescence assay...
January 6, 2018: Journal of Innate Immunity
Jorge Guerra-Varela, Maite Baz-Martínez, Sabela Da Silva-Álvarez, Ana Paula Losada, María Isabel Quiroga, Manuel Collado, Carmen Rivas, Laura Sánchez
The zebrafish, Danio rerio, has become recognized as a valuable model for infectious diseases. Here we evaluated the susceptibility of zebrafish to be infected with the mammalian vesicular stomatitis virus (VSV). Both zebrafish cells and embryos were highly susceptible to VSV infection. Mortalities exceeded 80% in infected embryos and were preceded by the invasion of the central nervous system by VSV. Live imaging of the infection with GFP-VSV as well as virus titration from infected fish confirmed the viral replication...
January 5, 2018: Zebrafish
Eunhye Kim, Hyunjhung Jhun, Joohee Kim, Unjoo Park, Seunghyun Jo, Areum Kwak, Sinae Kim, Tam T Nguyen, Yongsun Kang, Insoo Choi, Joongbok Lee, Heijun Kim, Younghyun Kim, Siyoung Lee, Soohyun Kim
Interferons (IFNs) have been known as antiviral genes and they are classified by type 1, type 2, and type 3 IFN. The type 1 IFN consists of IFNα, IFNβ, IFNτ, and IFNω whereas the type 2 IFN consists of only IFNγ, which is a key cytokine driving T helper cell type 1 immunity. IFNλ belongs to the type 3 IFN, which is also known as IL-28 and IL-29 possessing antiviral activities. Type 1 IFN is produced by viral infection whereas type 2 IFN is induced by mitogenic or antigenic T-cell stimuli. The IFNτ of bovine was first discovered in an ungulate ruminant recognition hormone...
December 2017: Immune Network
Camille Lévy, Fouzia Amirache, Anais Girard-Gagnepain, Cecilia Frecha, Francisco J Roman-Rodríguez, Ornellie Bernadin, Caroline Costa, Didier Nègre, Alejandra Gutierrez-Guerrero, Lenard S Vranckx, Isabelle Clerc, Naomi Taylor, Lars Thielecke, Kerstin Cornils, Juan A Bueren, Paula Rio, Rik Gijsbers, François-Loïc Cosset, Els Verhoeyen
Hematopoietic stem cell (HSC)-based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein-displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34+ (hCD34+) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34+ cells, whereas conventional vesicular stomatitis virus G (VSV-G)-LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor...
October 24, 2017: Blood Advances
Peili Hou, Guimin Zhao, Hongmei Wang, Chengqiang He, Yanjun Huan, Hongbin He
Bovine ephemeral fever virus (BEFV), identified as the causative pathogen of bovine ephemeral fever (BEF), is responsible for increasing numbers of epidemics/outbreaks and has a significant harmful effect on the livestock industry. Therefore, a rapid detection assay is imperative for BEFV diagnosis. In this study, we described the development of lateral-flow dipstick isothermal recombinase polymerase amplification (LFD-RPA) assays for detection of BEFV. RPA primers and LF probes were designed by targeting the specific G gene, and the amplification product can be visualized on a simple lateral flow dipstick with the naked eyes...
December 26, 2017: Molecular and Cellular Probes
Jiaoyu Shan, Binbin Zhao, Zhao Shan, Jia Nie, Rong Deng, Rui Xiong, Andy Tsun, Weiqi Pan, Hanzhi Zhao, Ling Chen, Ying Jin, Zhikang Qian, Kawing Lui, Rui Liang, Dan Li, Bing Sun, Dimitri Lavillette, Ke Xu, Bin Li
The histone demethylase LSD1 has been known as a key transcriptional coactivator for DNA viruses such as herpes virus. Inhibition of LSD1 was found to block viral genome transcription and lytic replication of DNA viruses. However, RNA virus genomes do not rely on chromatin structure and histone association, and the role of demethylase activity of LSD1 in RNA virus infections is not anticipated. Here, we identify that, contrary to its role in enhancing DNA virus replication, LSD1 limits RNA virus replication by demethylating and activating IFITM3 which is a host restriction factor for many RNA viruses...
December 27, 2017: PLoS Pathogens
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