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    Voluntary Wheel Running Does Not Alter Mortality to or Immunogenicity of Vaccinia Virus in Mice: A Pilot Study.
    Front Physiol 2017 5;8:1123. Epub 2018 Jan 5.
    Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, United States.
    Exercise has been shown to improve immune responses to viral infections and vaccines in several mouse models. However, previous pathogen studies have primarily used infections limited to the respiratory tract. Additionally, previous studies have utilized forced treadmill exercise paradigms, and voluntary wheel running (VWR) has been shown to have differential effects on the immune system in non-infection models. Read More

    Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments.
    PLoS One 2018 19;13(1):e0188453. Epub 2018 Jan 19.
    Department of Medical Microbiology & Immunology and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
    Edward Jenner and his contemporaries believed that his variolae vaccinae originated in horses and molecular analyses show that modern vaccinia virus (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based vaccine might provide a superior alternative. Since HPXV may be extinct and the only specimen of HPXV that has been identified is unavailable for investigation, we explored whether HPXV could be obtained by large-scale gene synthesis. Read More

    Vaccinia Virus in Blood Samples of Humans, Domestic and Wild Mammals in Brazil.
    Viruses 2018 Jan 18;10(1). Epub 2018 Jan 18.
    Faculdade de Medicina Veterinária e Zootecnia, UNESP-Universidade Estadual Paulista, Botucatu CEP 18618-970, Brazil.
    Outbreaks of Vaccinia virus (VACV) affecting cattle and humans have been reported in Brazil in the last 15 years, but the origin of outbreaks remains unknown. Although VACV DNA have been already detected in mice (Mus musculus), opossums (Didelphis albiventris) and dogs during VACV zoonotic outbreaks, no transmission to cattle or humans from any of these were reported during Brazilian outbreaks. In this work, we assessed the PCR positivity to VACV in blood samples of cows and other domestic mammals, wild rodents and other wild mammals, and humans from areas with or without VACV infection reports. Read More

    Identification of Poxvirus Genome Uncoating and DNA Replication Factors with Mutually Redundant Roles.
    J Virol 2018 Jan 17. Epub 2018 Jan 17.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA
    Genome uncoating is essential for replication of most viruses. For poxviruses, the process is divided into two stages: removal of the envelope allowing early gene expression, and breaching of the core wall allowing DNA release, replication and late gene expression. Subsequent studies showed that the host proteasome and the viral D5 protein, which has an essential role in DNA replication, are required for vaccinia virus (VACV) genome uncoating. Read More

    Characterizing the effects of insertion of a 5.2 kb region of a VACV genome, which contains known immune evasion genes, on MVA immunogenicity.
    Virus Res 2018 Jan 13. Epub 2018 Jan 13.
    Department of Microbiology, B103 Chemical and Life Science Building, 601 South Goodwin Avenue, University of Illinois, Urbana, IL 61801, USA. Electronic address:
    Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that is a popular vaccine vector candidate against many different pathogens. Its replication-restricted nature makes it a safe vaccine. However, higher doses or multiple boosts of MVA are necessary to elicit an immune response similar to wild-type VACV. Read More

    VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis.
    Cell Mol Life Sci 2018 Jan 16. Epub 2018 Jan 16.
    Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer-Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
    Regulation of cell division requires the integration of signals implicated in chromatin reorganization and coordination of its sequential changes in mitosis. Vaccinia-related kinase 1 (VRK1) and Aurora B (AURKB) are two nuclear kinases involved in different steps of cell division. We have studied whether there is any functional connection between these two nuclear kinases, which phosphorylate histone H3 in Thr3 and Ser10, respectively. Read More

    A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge.
    Sci Rep 2018 Jan 16;8(1):864. Epub 2018 Jan 16.
    Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
    Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013-2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV). Read More

    Functionally Convergent B Cell Receptor Sequences in Transgenic Rats Expressing a Human B Cell Repertoire in Response to Tetanus Toxoid and Measles Antigens.
    Front Immunol 2017 22;8:1834. Epub 2017 Dec 22.
    Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
    The identification and tracking of antigen-specific immunoglobulin (Ig) sequences within total Ig repertoires is central to high-throughput sequencing (HTS) studies of infections or vaccinations. In this context, public Ig sequences shared by different individuals exposed to the same antigen could be valuable markers for tracing back infections, measuring vaccine immunogenicity, and perhaps ultimately allow the reconstruction of the immunological history of an individual. Here, we immunized groups of transgenic rats expressing human Ig against tetanus toxoid (TT), Modified Vaccinia virus Ankara (MVA), measles virus hemagglutinin and fusion proteins expressed on MVA, and the environmental carcinogen benzo[a]pyrene, coupled to TT. Read More

    Lamin A/C augments Th1 differentiation and response against vaccinia virus and Leishmania major.
    Cell Death Dis 2018 Jan 8;9(1). Epub 2018 Jan 8.
    Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
    Differentiation of naive CD4+ T-cells into functionally distinct T helper (Th) subsets is critical to immunity against pathogen infection. Little is known about the role of signals emanating from the nuclear envelope for T-cell differentiation. The nuclear envelope protein lamin A/C is induced in naive CD4+ T-cells upon antigen recognition and acts as a link between the nucleus and the plasma membrane during T-cell activation. Read More

    Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating peptide.
    J Drug Target 2018 Jan 16:1-16. Epub 2018 Jan 16.
    b Zhejiang Reachall Pharmaceutical Co. Ltd , Zhejiang , PR China.
    Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumours. Here, we reported a novel tumour targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumour cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively. Read More

    p53-reactive T cells are associated with clinical benefit in patients with platinum-resistant epithelial ovarian cancer after treatment with a p53 vaccine and gemcitabine chemotherapy.
    Clin Cancer Res 2018 Jan 4. Epub 2018 Jan 4.
    Medical Oncology and Therapeutic Research, City of Hope.
    Purpose: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer.

    Experimental Design: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Read More

    A Model to Detect Autochthonous Group 1 and 2 Brazilian Vaccinia virus Coinfections: Development of a qPCR Tool for Diagnosis and Pathogenesis Studies.
    Viruses 2017 Dec 30;10(1). Epub 2017 Dec 30.
    Laboratório de Vírus, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil.
    Vaccinia virus (VACV) is the etiological agent of bovine vaccinia (BV), an emerging zoonosis that has been associated with economic losses and social effects. Despite increasing reports of BV outbreaks in Brazil, little is known about the biological interactions of Brazilian VACV (VACV-BR) isolates during coinfections; furthermore, there are no tools for the diagnosis of these coinfections. In this study, a tool to co-detect two variants of VACV was developed to provide new information regarding the pathogenesis, virulence profile, and viral spread during coinfection with VACV-BR isolates. Read More

    E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox.
    Viruses 2018 Jan 4;10(1). Epub 2018 Jan 4.
    Lehrstuhl für Virologie, Institut für Infektionsmedizin und Zoonosen, Ludwig-Maximilians-Universität München, 80539 Munich, Germany.
    The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Read More

    Evaluation of Viral Genome Copies Within Viral Factories on Different DNA Viruses.
    J Histochem Cytochem 2018 Jan 1:22155417749490. Epub 2018 Jan 1.
    Laboratory of Cell Biology and Virology, Institute of Molecular Biology NAS RA, Yerevan, Armenia.
    This article describes a simple method of measuring the number of viral genomes within viral factories. For this purpose, we use three DNA viruses replicating in the cytoplasm of the infected cells: wild-type African swine fever virus (ASFV)-Georgia 2007, culture-adapted type ASFV-BA71V, and Vaccinia virus (VV). The measurements are conducted in three steps. Read More

    Long-lived plasma cells in human bone marrow can be either CD19+ or CD19.
    Blood Adv 2017 May 19;1(13):835-838. Epub 2017 May 19.
    Department of Microbiology and Immunology, Institute of Biomedicine, and.
    Long-lived plasma cells secreting vaccinia-specific antibodies are detected in human bone marrow >35 years after the eradication of smallpox.Long-lived plasma cells secreting vaccinia-specific antibodies are still able to express the B-lymphocyte antigen CD19. Read More

    High Initial Sputter Rate Found for Vaccinia Virions Using Isotopic Labeling, NanoSIMS, and AFM.
    Anal Chem 2018 Jan 19. Epub 2018 Jan 19.
    Department of Molecular Genetics and Microbiology, University of Florida , Gainesville, Florida 32610, United States.
    High-lateral-resolution secondary ion mass spectrometry (SIMS) has the potential to provide functional and depth resolved information from small biological structures, such as viral particles (virions) and phage, but sputter rate and sensitivity are not characterized at shallow depths relevant to these structures. Here we combine stable isotope labeling of the DNA of vaccinia virions with correlated SIMS imaging depth profiling and atomic force microscopy (AFM) to develop a nonlinear, nonequilibrium sputter rate model for the virions and validate the model on the basis of reconstructing the location of the DNA within individual virions. Our experiments with a Cs+ beam show an unexpectedly high initial sputter rate (∼100 um2·nm·pA-1·s-1) with a rapid decline to an asymptotic rate of 0. Read More

    CD70 encoded by modified vaccinia virus Ankara enhances CD8 T cell dependent protective immunity in MHC class II-deficient mice.
    Immunology 2017 Dec 27. Epub 2017 Dec 27.
    Bavarian Nordic GmbH, Fraunhoferstraße 13, 82152, Martinsried, Germany.
    The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen-presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T cell receptor complex a plethora of co-stimulatory signals not only ensures a proper T cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The TNF receptor/ligand pair CD27/CD70 gained a lot of attraction due to its key role in regulating T cell activation, survival, differentiation, and maintenance, especially in the course of viral infections and cancer. Read More

    Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways.
    Viruses 2017 Dec 27;10(1). Epub 2017 Dec 27.
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
    An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC) poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. Read More

    Type I interferon receptor-signaling delays Kupffer cell replenishment during acute fulminant viral hepatitis.
    J Hepatol 2017 Dec 2. Epub 2017 Dec 2.
    Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hanover Medical School and the Helmholtz Centre for Infection Research, Brunswick, Germany. Electronic address:
    Background And Aim: Virus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Here we dissected the impact of locally induced IFN-I responses on myeloid cell function and hepatocytes during acute liver inflammation. Read More

    Ocular Vaccinia Infection in Dairy Worker, Brazil.
    Emerg Infect Dis 2018 Jan;24(1):161-162
    We studied a clinical case of vaccinia virus that caused an ocular manifestation in a dairy worker in Brazil. Biologic and molecular analyses identified a co-infection with 2 isolates from different Brazilian vaccinia virus phylogenetic groups. Read More

    Amplification of oncolytic vaccinia virus widespread tumor cell killing by sunitinib through multiple mechanisms.
    Cancer Res 2017 Dec 19. Epub 2017 Dec 19.
    Comprehensive Cancer Center and Dept of Anatomy, Univ of California, San Francisco
    Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors (PNET) that developed spontaneously and progress as in humans. Read More

    Vaccination with Combination DNA and Virus-Like Particles Enhances Humoral and Cellular Immune Responses upon Boost with Recombinant Modified Vaccinia Virus Ankara Expressing Human Immunodeficiency Virus Envelope Proteins.
    Vaccines (Basel) 2017 Dec 19;5(4). Epub 2017 Dec 19.
    Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
    Heterologous prime boost with DNA and recombinant modified vaccinia virus Ankara (rMVA) vaccines is considered as a promising vaccination approach against human immunodeficiency virus (HIV-1). To further enhance the efficacy of DNA-rMVA vaccination, we investigated humoral and cellular immune responses in mice after three sequential immunizations with DNA, a combination of DNA and virus-like particles (VLP), and rMVA expressing HIV-1 89.6 gp120 envelope proteins (Env). Read More

    A Robust System for Production of Superabundant VP1 Recombinant AAV Vectors.
    Mol Ther Methods Clin Dev 2017 Dec 7;7:146-156. Epub 2017 Nov 7.
    School of Biomedical Sciences, Huaqiao University, Quanzhou, Fujian, China.
    Recombinant adeno-associated viral (rAAV) vectors have been widely used in human gene therapy. One major impediment to its broad application is the inability to produce high-quality vectors in mass quantity. Here, an efficient and scalable suspension cell culture system for the production of rAAV vectors is described. Read More

    Protection of Mice from Lethal Vaccinia Virus Infection by Vaccinia Virus Protein Subunits with a CpG Adjuvant.
    Viruses 2017 Dec 9;9(12). Epub 2017 Dec 9.
    Chemical, Biological & Radiological Division, Dstl Porton Down, Salisbury SP4 0JQ, UK.
    Smallpox vaccination carries a high risk of adverse events in recipients with a variety of contra-indications for live vaccines. Although alternative non-replicating vaccines have been described in the form of replication-deficient vaccine viruses, DNA vaccines, and subunit vaccines, these are less efficacious than replicating vaccines in animal models. DNA and subunit vaccines in particular have not been shown to give equivalent protection to the traditional replicating smallpox vaccine. Read More

    Recombinant Vaccinia virus-coded interferon inhibitor B18R: Expression, refolding and a use in a mammalian expression system with a RNA-vector.
    PLoS One 2017 7;12(12):e0189308. Epub 2017 Dec 7.
    National Center for Biotechnology, Astana, Kazakhstan.
    B18R protein of Vaccinia virus binds to type I interferons and inhibits activation of interferon-mediated signal transduction. Cells which have unimpaired interferon signaling such as primary cell cultures or some industrially important cell lines are capable of development of an antiviral state. An establishment of the antiviral state limits replication of RNA-viruses and can suppress replication of RNA vectors. Read More

    Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial.
    Front Immunol 2017 20;8:1551. Epub 2017 Nov 20.
    Medical Research Council Unit, Fajara, Gambia.
    Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines. Read More

    Antiviral activity and metal ion-binding properties of some 2-hydroxy-3-methoxyphenyl acylhydrazones.
    Biometals 2018 Feb 5;31(1):81-89. Epub 2017 Dec 5.
    Rega Institute for Medical Research, KU Leuven - University of Leuven, 3000, Louvain, Belgium.
    Here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and African Green monkey kidney cells). Read More

    Complete regression of cutaneous metastases with systemic immune response in a patient with triple negative breast cancer receiving p53MVA vaccine with pembrolizumab.
    Oncoimmunology 2017 11;6(12):e1363138. Epub 2017 Aug 11.
    Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
    A heavily pretreated patient with triple negative breast cancer distinguished by cutaneous metastases received p53MVA vaccine in combination with pembrolizumab. Her cutaneous metastases regressed and after 2 cycles of therapy, a skin biopsy showed a complete pathological response. Systemic response was confirmed with restaging CT and bone scans. Read More

    Suppression of Poxvirus Replication by Resveratrol.
    Front Microbiol 2017 17;8:2196. Epub 2017 Nov 17.
    Division of Biology, Kansas State University, Manhattan, KS, United States.
    Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. Read More

    Enigmatic origin of the poxvirus membrane from the endoplasmic reticulum shown by 3D imaging of vaccinia virus assembly mutants.
    Proc Natl Acad Sci U S A 2017 Dec 4;114(51):E11001-E11009. Epub 2017 Dec 4.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
    The long-standing inability to visualize connections between poxvirus membranes and cellular organelles has led to uncertainty regarding the origin of the viral membrane. Indeed, there has been speculation that viral membranes form de novo in cytoplasmic factories. Another possibility, that the connections are too short-lived to be captured by microscopy during a normal infection, motivated us to identify and characterize virus mutants that are arrested in assembly. Read More

    Reply to "Bioinformatics Analysis of Differential Innate Immune Signaling in Macrophages by Wild-Type Vaccinia Mature Virus and a Mutant Virus with a Deletion of the A26 Protein".
    J Virol 2017 Dec 30;91(24). Epub 2017 Nov 30.
    Molecular Cell Biology, Taiwan International Graduate Program, Graduate Institute of Life Sciences, National Defense Medical Center, Academia Sinica, Taipei, Taiwan, Republic of China

    Immunogenicity of recombinant vaccinia virus vaccines co-expressing GP3/GP5 of European PRRSV and Cap protein of PCV2 in pigs.
    Appl Microbiol Biotechnol 2018 Feb 30;102(3):1145-1154. Epub 2017 Nov 30.
    Medical College, Yanbian University, Yanji, 133002, China.
    Porcine reproductive and respiratory syndrome (PRRS) is almost always caused by the North American strain of PRRS virus (PRRSV) in China; the European genotype of PRRSV has emerged in China. The mixed infection of PRRSV and Porcine circovirus type 2 virus (PCV2) are always found in pigs and PRRSV-augmented PCV2 replication and serious clinical symptoms. Current vaccines cannot protect mixed European PRRSV and PCV2 infections. Read More

    Bioluminescence imaging of a tumor-selective, thymidine kinase-defective vaccinia virus Guang9 strain after intratumoral or intraperitoneal administration in mice.
    Oncotarget 2017 Oct 8;8(51):88708-88718. Epub 2017 Sep 8.
    Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
    Vaccinia virus has been used as an oncolytic virus because of its capacity to preferentially infect tumors rather than normal tissues. The vaccinia Tian Tan strain, used as a vaccine against smallpox for millions of people in China, is a promising candidate for cancer therapy. In this study, we constructed an attenuated Tian Tan strain of Guang9 with a disrupted thymidine kinase gene to enhance tumor selectivity and an inserted firefly luciferase to monitor the viral distribution by in vivo bioluminescence imaging. Read More

    Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization.
    Virology 2018 Jan 22;514:106-117. Epub 2017 Nov 22.
    Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
    HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessibility to antibodies. Using a vaccinia prime/protein boost protocol in mice, we explored the immunologic effects of mutations in the Env cytoplasmic tail (CT) that increased surface expression, including partial truncation and ablation of a tyrosine-dependent endocytosis motif. Read More

    The effects of diets enriched in omega-3 polyunsaturated fatty acids on systemic vaccinia virus infection.
    Sci Rep 2017 Nov 22;7(1):15999. Epub 2017 Nov 22.
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA.
    Omega-3 polyunsaturated fatty acids (PUFA, n-3 fatty acids), the key components of fish and flaxseed oils, are increasingly consumed by the public because of their potential health benefits and are available by prescription for hypertriglyceridemia. However, numerous studies have shown that these compounds are immunoregulatory and immunosuppressive and thus may increase susceptibility to infection. In this study, we tested the effects of the amount of fat and the types of fatty acid in the diet on infection by vaccinia virus, an acute infection that begins in the respiratory tract and spreads by viremia to internal organs. Read More

    Flow Virometry: a Powerful Tool To Functionally Characterize Viruses.
    J Virol 2018 Feb 17;92(3). Epub 2018 Jan 17.
    Department of Pathology and Cell Biology, University of Montreal, Montreal, Québec, Canada
    For several decades, flow cytometry has been a common approach to analyze cells and sort them to near-purity. It enables one to probe inner cellular molecules, surface receptors, or infected cells. However, the analysis of smaller entities such as viruses and exocytic vesicles has been more difficult but is becoming mainstream. Read More

    Generation of an Attenuated Tiantan Vaccinia Virus Strain by Deletion of Multiple Genes.
    Front Cell Infect Microbiol 2017 31;7:462. Epub 2017 Oct 31.
    Medical College, Yanbian University, Yanji, China.
    An attenuated vaccinia virus-MVTTEAB-was constructed by deletion of non-essential gene segments related to the immunomodulatory and virulence functions of the vaccinia virus Tiantan strain (VVTT). The shuttle plasmids pTC-EGFP, pTE-EGFP, pTA35-EGFP, pTB-EGFP, and pTA66-EGFP were constructed and combined with the early and late strong promoter pE/L and EGFP as an exogenous selectable marker. Then, through the homologous recombination technology and Cre/loxP system, the following gene fragments were gradually knocked out one by one: TC7L-TK2L, TE3L, TA35R, TB13R, and TA66R. Read More

    Insertion of the Type-I IFN Decoy Receptor B18R in a miRNA-Tagged Semliki Forest Virus Improves Oncolytic Capacity but Results in Neurotoxicity.
    Mol Ther Oncolytics 2017 Dec 5;7:67-75. Epub 2017 Oct 5.
    Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Oncolytic Semliki Forest virus (SFV) has been suggested as a potential candidate for the treatment of glioblastoma and neuroblastoma. However, the oncolytic capacity of SFV is restricted by the anti-viral type-I interferon (IFN) response. The aim of this study was to increase the oncolytic capacity of a microRNA target tagged SFV against glioblastoma by arming it with the Vaccinia-virus-encoded type-I IFN decoy receptor B18R (SFV4B18RmiRT) to neutralize type-I IFN response. Read More

    Dairy production practices and associated risks for bovine vaccinia exposure in cattle, Brazil.
    New Microbes New Infect 2017 Nov 16;20:43-50. Epub 2017 Aug 16.
    Departamento de Microbiologia, Brazil.
    A cross-sectional serosurvey was performed to identify environmental features or practices of dairy farms associated with risk for exposure to vaccinia-like viruses in dairy cattle in Brazil. Sera from 103 cows from 18 farms in Minas Gerais state were examined for Orthopoxvirus-neutralizing antibodies. A database of 243 binary or multiple-selection categorical variables regarding the physical features and surrounding ecology of each property was obtained. Read More

    Vaccinia Virus Natural Infections in Brazil: The Good, the Bad, and the Ugly.
    Viruses 2017 Nov 15;9(11). Epub 2017 Nov 15.
    Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
    The orthopoxviruses (OPV) comprise several emerging viruses with great importance to human and veterinary medicine, including vaccinia virus (VACV), which causes outbreaks of bovine vaccinia (BV) in South America. Historically, VACV is the most comprehensively studied virus, however, its origin and natural hosts remain unknown. VACV was the primary component of the smallpox vaccine, largely used during the smallpox eradication campaign. Read More

    Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine.
    Vaccine 2017 Dec 11;35(52):7222-7230. Epub 2017 Nov 11.
    Centre for Biological Threats and Special Pathogens 1 - Highly Pathogenic Viruses & German Consultant Laboratory for Poxviruses & WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany.
    For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. Read More

    ING4 expressing oncolytic vaccinia virus promotes anti-tumor efficiency and synergizes with gemcitabine in pancreatic cancer.
    Oncotarget 2017 Oct 20;8(47):82728-82739. Epub 2017 Sep 20.
    Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, P. R. China.
    With no effective treatments available for most pancreatic cancer patients, pancreatic cancer continues to be one of the most difficult malignancies to treat. Oncolytic virus mediated-gene therapy has exhibited ubiquitous antitumor potential. In this study, we constructed a novel oncolytic vaccinia virus harboring the inhibitor of growth family member 4 gene (VV-ING4) to investigate its therapeutic efficacy alone or in combination with gemcitabine against pancreatic cancer cells in vitro and in vivo. Read More

    The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding.
    Nat Commun 2017 Nov 13;8(1):1455. Epub 2017 Nov 13.
    Unité de Virologie, Institut de Recherche Biomédicale des Armées, BP 73, 91223, Brétigny-sur-Orge Cedex, France.
    Vaccinia virus (VACV), the prototype member of the Poxviridae, replicates in the cytoplasm of an infected cell. The catalytic subunit of the DNA polymerase E9 binds the heterodimeric processivity factor A20/D4 to form the functional polymerase holoenzyme. Here we present the crystal structure of full-length E9 at 2. Read More

    Structure-function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8.
    J Biol Chem 2018 Jan 9;293(1):390-401. Epub 2017 Nov 9.
    From the Divisions of Cell Biology,
    Vaccinia virus (VACV) envelope protein D8 is one of three glycosaminoglycan adhesion molecules and binds to the linear polysaccharide chondroitin sulfate (CS). D8 is also a target for neutralizing antibody responses that are elicited by the smallpox vaccine, which has enabled the first eradication of a human viral pathogen and is a useful model for studying antibody responses. However, to date, VACV epitopes targeted by human antibodies have not been characterized at atomic resolution. Read More

    A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model.
    Sci Rep 2017 Nov 7;7(1):14769. Epub 2017 Nov 7.
    Geovax, Smyrna, GA, United States.
    Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Read More

    Enhanced directional cell migration induced by vaccinia virus on a microfluidic-based multi-shear cell migration assay platform.
    Integr Biol (Camb) 2017 Dec;9(12):903-911
    Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, P. R. China.
    Virus-induced cell migration plays important roles in the direct and rapid spread of virus particles. As cell migration is also regulated by shear stress, it is necessary to explore the cell migration behavior influenced by multiple factors including a virus and shear stress. In this report, a three-layer microfluidic chip with symmetric channels was designed and fabricated to investigate vaccinia virus-induced cell migration in different shear stress environments. Read More

    Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?
    Viruses 2017 Oct 29;9(11). Epub 2017 Oct 29.
    Molecular Inflammation Research Group, Institute of Medical Biology, University i Tromsø (UiT)-The Arctic University of Norway, N-9037 Tromso, Norway.
    Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, animals and the environment. MVA and recombinant MVA are widely believed to pose low or negligible risk to ecosystem health. Read More

    High expression of VRK1 is related to poor prognosis in glioma.
    Pathol Res Pract 2017 Oct 18. Epub 2017 Oct 18.
    Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, 215123, PR China. Electronic address:
    Vaccinia-related kinase 1 (VRK1) is a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases, which phosphorylates several transcription factors and has been postulated to be involved in regulation of cell proliferation. However, it remains unclear whether aberrant expression of VRK1 is related to the development of glioma. In this study, we aimed to investigate the clinical significance of VRK1 expression in human glioma and its biological function in glioma cells. Read More

    Vaccinia Related Kinase 2 (VRK2) expression in neurological disorders: schizophrenia, epilepsy and multiple sclerosis.
    Mult Scler Relat Disord 2017 Oct 25;19:15-19. Epub 2017 Oct 25.
    Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, PO Box 1985717443, Tehran, Iran; Urogenital Stem Cell Research Center, Shahid Labbafi Nejad Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:
    Background: Schizophrenia (SCZ), epilepsy and Multiple Sclerosis (MS) are neurological disorders with increasing prevalence disturb the patients' lives and are regarded as burdens to the society. As multifactorial disorders, genetic susceptibility factors are involved in their pathogenesis. The Vaccinia-Related Kinase 2 (VRK2) gene codes for a serine threonine kinase recently reported to be contributed in the pathogenesis of some neurological disorders. Read More

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