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    Qualitative differences in cellular immunogenicity elicited by hepatitis C virus T-Cell vaccines employing prime-boost regimens.
    PLoS One 2017 21;12(7):e0181578. Epub 2017 Jul 21.
    Laboratory of Hepatitis Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD United States of America.
    T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. Read More

    Tissue Plasminogen Activator (tPA) Signal Sequence Enhances Immunogenicity of MVA-Based Vaccine Against Tuberculosis.
    Immunol Lett 2017 Jul 17. Epub 2017 Jul 17.
    National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, PR China; Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Science, Jilin University, Changchun 130012, PR China. Electronic address:
    Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines. Read More

    Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults.
    PLoS One 2017 20;12(7):e0179597. Epub 2017 Jul 20.
    Department of Surgery, Duke Human Vaccine Institute, Durham, North Carolina, United States of America.
    Background: A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env.

    Methods: Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively. Read More

    Vaccinia virus and Cowpox virus are not susceptible to the interferon-induced antiviral protein MxA.
    PLoS One 2017 20;12(7):e0181459. Epub 2017 Jul 20.
    Departamento de Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (I.N.I.A.), Madrid, Spain.
    MxA protein is expressed in response to type I and type III Interferon and constitute an important antiviral factor with broad antiviral activity to diverse RNA viruses. In addition, some studies expand the range of MxA antiviral activity to include particular DNA viruses like Monkeypox virus (MPXV) and African Swine Fever virus (ASFV). However, a broad profile of activity of MxA to large DNA viruses has not been established to date. Read More

    Species specificity of vaccinia virus complement control protein towards bovine classical pathway is governed primarily by direct interaction of its acidic residues with factor I.
    J Virol 2017 Jul 19. Epub 2017 Jul 19.
    Complement Biology Laboratory, National Centre for Cell Science, S. P. Pune University Campus, Ganeshkhind, Pune 411007, India
    Poxviruses display species tropism - variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. Consistent with this, variola virus complement regulator SPICE exhibit selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator VCP display selectivity in inhibiting the bovine alternative complement pathway. In the present study, we examined the species-specificity of VCP and SPICE towards the classical pathway (CP). Read More

    HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV.
    Heliyon 2017 Jun 29;3(6):e00339. Epub 2017 Jun 29.
    Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
    Background: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic.

    Methods: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated. Read More

    Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology.
    Mol Ther 2017 Jul 15. Epub 2017 Jul 15.
    Experimental Therapeutics Laboratory, Hanson Institute and Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia; Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia. Electronic address:
    Vaccinia-based systems have been extensively explored for the development of recombinant vaccines. Herein we describe an innovative vaccinia virus (VACV)-derived vaccine platform technology termed Sementis Copenhagen Vector (SCV), which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene D13L. A SCV cell substrate line was developed for SCV vaccine production by engineering CHO cells to express D13 and the VACV host-range factor CP77, because CHO cells are routinely used for manufacture of biologics. Read More

    Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA prime - Modified Vaccinia Ankara (MVA) boost HIV-1 vaccine regimen.
    J Virol 2017 Jul 12. Epub 2017 Jul 12.
    Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany
    Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. Read More

    Multisubunit DNA-Dependent RNA Polymerases from Vaccinia Virus and Other Nucleocytoplasmic Large-DNA Viruses: Impressions from the Age of Structure.
    Microbiol Mol Biol Rev 2017 Sep 12;81(3). Epub 2017 Jul 12.
    Department of Molecular Biology & Biochemisty, University of California-Irvine, Irvine, California, USA
    The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus. Read More

    Characterization of Eptesipoxvirus, a novel poxvirus from a microchiropteran bat.
    Virus Genes 2017 Jul 6. Epub 2017 Jul 6.
    Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
    The genome of Eptesipoxvirus (EPTV) is the first poxvirus genome isolated from a microbat. The 176,688 nt sequence, which is believed to encompass the complete coding region of the virus, is 67% A+T and is predicted to encode 191 genes. 11 of these genes have no counterpart in GenBank and are therefore unique to EPTV. Read More

    Clin Cancer Res 2017 Jul 5. Epub 2017 Jul 5.
    Research & Development, StemImmune Inc.
    Purpose: Pre-clinical models have shown that the effectiveness of GL-ONC1, a modified

    oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study

    was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy

    to patients with primary, non-metastatic head and neck cancer.

    EXPERIMENTAL DESIGN: Patients with locoregionally advanced unresected, non-metastatic

    carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were

    treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and

    chemotherapy. Read More

    Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies.
    Antiviral Res 2017 Jul 1;145:1-5. Epub 2017 Jul 1.
    Department of Pediatrics, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, 35233-1711, USA.
    Cell culture antiviral experiments were conducted in order to understand the relationship between percentage data generated by plaque reduction (PR) and logarithmic data derived by virus yield reduction (VYR) assays, using three-dimensional MacSynergy II software. The relationship between percentage and logarithmic data has not been investigated previously. Interpretation of drug-drug interactions is based on a Volume of Synergy (VS) calculation, which can be positive (synergy), negative (antagonistic), or neutral (no or minimal interaction). Read More

    Virtual screening, synthesis and biological evaluation of DNA intercalating antiviral agents.
    Bioorg Med Chem Lett 2017 Jun 13. Epub 2017 Jun 13.
    Laboratoire de Chemoinformatique, (UMR 7140 CNRS/UniStra), Université de Strasbourg, 4, rue B. Pascal, Strasbourg 67000, France; Federal University of Kazan, Kremlevskaya str., 18, Kazan, Russia. Electronic address:
    This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators. Read More

    Protein- and Modified Vaccinia virus Ankara-based Influenza Virus Nucleoprotein Vaccines are Differentially Immunogenic in BALB/c Mice.
    Clin Exp Immunol 2017 Jun 30. Epub 2017 Jun 30.
    Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands.
    Because of the high variability of seasonal influenza viruses and the eminent threat of influenza viruses with pandemic potential, there is great interest in the development of vaccines that induce broadly protective immunity. Most likely, broadly protective influenza vaccines are based on conserved proteins, such as nucleoprotein (NP). NP is a vaccine target of interest since it has been shown to induce cross-reactive antibody and T cell responses. Read More

    Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives.
    J Virol 2017 Jun 28. Epub 2017 Jun 28.
    Institute of Biochemistry, ETH Zurich
    Virus infection of humans and livestock can be devastating for individuals and populations, sometimes resulting in large economic and societal impact. Prevention of virus disease by vaccination or anti-viral agents is difficult to achieve. A notable exception was the eradication of human smallpox by vaccination over 30 years ago. Read More

    Differential innate immune signaling in macrophages by wild type vaccinia mature virus and a mutant virus deleting A26 protein.
    J Virol 2017 Jun 28. Epub 2017 Jun 28.
    Molecular Cell Biology, Taiwan International Graduate Program, Graduate Institute of Life Sciences, National Defense Medical Center,
    The Western Reserve (WR) strain of mature vaccinia virus contains an A26 envelope protein that mediates virus binding to cell surface laminin and subsequent endocytic entry into HeLa cells. Removal of A26 protein from mature virus generates a mutant WRΔA26 that enters HeLa cells through plasma membrane fusion. Here, we infected murine bone marrow-derived macrophages (BMDM) with wild-type WR and WRΔA26 and analyzed viral gene expression and cellular innate immune signaling. Read More

    Enhanced light microscopy visualization of virus particles from Zika virus to filamentous ebolaviruses.
    PLoS One 2017 26;12(6):e0179728. Epub 2017 Jun 26.
    Department of Microbiology, Boston University School of Medicine, Boston, MA, United States of America.
    Light microscopy is a powerful tool in the detection and analysis of parasites, fungi, and prokaryotes, but has been challenging to use for the detection of individual virus particles. Unlabeled virus particles are too small to be visualized using standard visible light microscopy. Characterization of virus particles is typically performed using higher resolution approaches such as electron microscopy or atomic force microscopy. Read More

    Vaccinia virus detection in dairy products made with milk from experimentally infected cows.
    Transbound Emerg Dis 2017 Jun 26. Epub 2017 Jun 26.
    Laboratório de Pesquisa em Virologia Animal, Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
    Vaccinia virus (VACV) is the agent of bovine vaccinia (BV), an emerging zoonosis that causes exanthematic lesions on the teats of dairy cows and on the hands of milkers. The virus has been detected in the milk of naturally infected cows. The objective of this study was to investigate and quantify VACV DNA as well as the presence of infectious virus particles in samples of cheese curd, cheese whey and pasteurized milk produced using milk from cows experimentally inoculated with VACV-GP2, a Brazilian isolate of VACV (VACV-BR). Read More

    VRK2A is an A-type lamin-dependent nuclear envelope kinase that phosphorylates BAF.
    Mol Biol Cell 2017 Jun 21. Epub 2017 Jun 21.
    *Sanford Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104
    The nuclear envelope (NE) is critical for numerous fundamental cellular functions and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis of lamin-A, Sun2 and a minimal INM-targeting motif. These studies identified vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM. Read More

    Going Against The Tide: Selective Cellular Protein Synthesis During Virally Induced Host Shutoff.
    J Virol 2017 Jun 21. Epub 2017 Jun 21.
    Division of Biology, Kansas State University, Manhattan, KS, 66506
    Many viral infections cause host shutoff, a state in which host protein synthesis is globally inhibited. Emerging evidence from vaccinia and influenza A virus infections indicates that subsets of cellular proteins are resistant to host shutoff and continue to be synthesized. Remarkably, the proteins of oxidative phosphorylation, the cellular energy generating machinery, are selectively synthesized in both cases. Read More

    Antiviral Activity of Fridericia formosa (Bureau) L. G. Lohmann (Bignoniaceae) Extracts and Constituents.
    J Trop Med 2017 29;2017:6106959. Epub 2017 May 29.
    Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil.
    A phytochemical study of Fridericia formosa (Bignoniaceae) ethanol extracts of leaves, stems, and fruits was guided by in vitro assays against vaccinia virus Western Reserve (VACV-WR), human herpes virus 1 (HSV-1), murine encephalomyocarditis virus (EMCV), and dengue virus type 2 (DENV-2) by the MTT method. All the ethanol extracts were active against DENV-2, HSV-1, and VACV-WR with best results for the fruits extract against DENV-2 (SI > 38.2). Read More

    Impact of isoniazid preventive therapy on the evaluation of long-term effectiveness of infant MVA85A vaccination.
    Int J Tuberc Lung Dis 2017 Jul;21(7):778-783
    South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
    Setting: South Africa.

    Objective: To evaluate the long-term effectiveness of infant modified vaccinia Ankara virus-expressing antigen 85A (MVA85A) vaccination against tuberculosis (TB).

    Design: We analysed data from a double-blind randomised placebo-controlled Phase 2b MVA85A infant TB vaccine trial (2009-2012), with extended post-trial follow-up (2012-2014). Read More

    Vaccinia virus egress mediated by virus protein A36 is reliant on the F12 protein.
    J Gen Virol 2017 Jun 20;98(6):1500-1514. Epub 2017 Jun 20.
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
    Egress of vaccinia virus from its host cell is mediated by the microtubule-associated motor kinesin-1, and three viral proteins, A36 and the F12/E2 complex, have been implicated in this process. Deletion of F12 expression causes a more severe reduction in egress than deletion of A36 but whether these proteins are involved in the same or different mechanisms of kinesin-1 recruitment is unknown. Here it is shown that a virus lacking both proteins forms a smaller plaque than mutants lacking either gene alone, indicating non-redundant functions. Read More

    Vaccination with a codon-optimized A27L-containing plasmid decreases virus replication and dissemination after vaccinia virus challenge.
    Vaccine 2017 Jun 16. Epub 2017 Jun 16.
    Department of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, School of Medicine, San Juan, PR 00936, United States. Electronic address:
    Smallpox is a disease caused by Variola virus (VARV). Although eradicated by WHO in 1980, the threat of using VARV on a bioterror attack has increased. The current smallpox vaccine ACAM2000, which consists of live vaccinia virus (VACV), causes complications in individuals with a compromised immune system or with previously reported skin diseases. Read More

    Ectromelia virus accumulates less double-stranded RNA compared to vaccinia virus in BS-C-1 cells.
    Virology 2017 Sep;509:98-111
    Department of Biology, Albright College, Reading, PA, USA. Electronic address:
    Most orthopoxviruses, including vaccinia virus (VACV), contain genes in the E3L and K3L families. The protein products of these genes have been shown to combat PKR, a host defense pathway. Interestingly, ectromelia virus (ECTV) contains an E3L ortholog but does not possess an intact K3L gene. Read More

    Induction, treatment and prevention of eczema vaccinatum in atopic dermatitis mouse models.
    Vaccine 2017 Jul 20;35(33):4245-4254. Epub 2017 Jun 20.
    Department of Infectious Diseases, Israel Institute for Biological Research (IIBR), Ness-Ziona, Israel. Electronic address:
    Eczema vaccinatum is a severe and occasionally lethal complication of smallpox vaccine, characterized by systemic viral dissemination, distant from the initial inoculation site of the vaccine. A major risk factor for eczema vaccinatum is a background of atopic dermatitis, a chronic, common allergic, relapsing disorder, manifested by dry and inflamed skin, itchy rash, Th2 biased immune response and hypersensitivity to various antigens. Unlike the severe manifestations of eczema vaccinatum in humans, current models present only mild symptoms that limits examination of potential therapeutics for eczema vaccinatum. Read More

    c-Jun integrates signals from both MEK/ERK and MKK/JNK pathways upon vaccinia virus infection.
    Arch Virol 2017 Jun 15. Epub 2017 Jun 15.
    Signal Transduction Group/Orthopoxviruses, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
    Usurpation of the host's signalling pathways is a common strategy employed by viruses to promote their successful replication. Here we show that infection with the orthopoxvirus vaccinia virus (VACV) leads to sustained stimulation of c-Jun activity during the entire infective cycle. This stimulation is temporally regulated through MEK/ERK or MKK/JNK pathways, i. Read More

    Vaccinia virus A11 is required for membrane rupture and viral membrane assembly.
    Cell Microbiol 2017 Jun 15. Epub 2017 Jun 15.
    EM Core Facility & Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.
    Although most enveloped viruses acquire their membrane from the host by budding or by a wrapping process, collective data argue that nucleocytoplasmic large DNA viruses (NCLDVs) may be an exception. The prototype member of NCLDVs, vaccinia virus (VACV) may induce rupture of endoplasmic-reticulum-derived membranes to build an open-membrane sphere that closes after DNA uptake. This unconventional membrane assembly pathway is also used by at least 3 other members of the NCLDVs. Read More

    Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies.
    JCI Insight 2017 Jun 15;2(12). Epub 2017 Jun 15.
    The Jenner Institute, University of Oxford, Oxford, United Kingdom.
    Background: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Read More

    A systemic macrophage response is required to contain a peripheral poxvirus infection.
    PLoS Pathog 2017 Jun 14;13(6):e1006435. Epub 2017 Jun 14.
    Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, PA, United States of America.
    The goal of the innate immune system is to reduce pathogen spread prior to the initiation of an effective adaptive immune response. Following an infection at a peripheral site, virus typically drains through the lymph to the lymph node prior to entering the blood stream and being systemically disseminated. Therefore, there are three distinct spatial checkpoints at which intervention to prevent systemic spread of virus can occur, namely: 1) the site of infection, 2) the draining lymph node via filtration of lymph or 3) the systemic level via organs that filter the blood. Read More

    Chemovirotherapy of Pancreatic Adenocarcinoma by Combining Oncolytic Vaccinia Virus GLV-1h68 with nab-Paclitaxel Plus Gemcitabine.
    Mol Ther Oncolytics 2017 Sep 19;6:10-21. Epub 2017 Apr 19.
    Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
    Oncolytic viruses have proven their therapeutic potential against a variety of different tumor entities both in vitro and in vivo. Their ability to selectively infect and lyse tumor cells, while sparing healthy tissues, makes them favorable agents for tumor-specific treatment approaches. Particularly, the addition of virotherapeutics to already established chemotherapy protocols (so-called chemovirotherapy) is of major interest. Read More

    Comparative Efficacy of Intramuscular and Scarification Routes of Administration of Live Smallpox Vaccine in a Murine Challenge Model.
    Vaccine 2017 Jul 9;35(31):3889-3896. Epub 2017 Jun 9.
    CBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UK; The Pirbright Institute, Ash Road, Woking GU24 0NF, UK. Electronic address:
    In recent years concern has mounted regarding the possibility of a re-emergence of smallpox through biowarfare or bioterrorism. There is also concern over the incidence of human monkeypox in endemic areas and the potential for monkeypox to be accidentally transported to non-endemic areas. In the event of re-emergence of smallpox or emergence of monkeypox, the accepted route of administration for live replicating smallpox vaccine is dermal scarification, which generates a virus-shedding lesion that persists for several days at the vaccination site. Read More

    Classification of Cowpox Viruses into Several Distinct Clades and Identification of a Novel Lineage.
    Viruses 2017 Jun 10;9(6). Epub 2017 Jun 10.
    Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald, Germany.
    Cowpox virus (CPXV) was considered as uniform species within the genus Orthopoxvirus (OPV). Previous phylogenetic analysis indicated that CPXV is polyphyletic and isolates may cluster into different clades with two of these clades showing genetic similarities to either variola (VARV) or vaccinia viruses (VACV). Further analyses were initiated to assess both the genetic diversity and the evolutionary background of circulating CPXVs. Read More

    Anti-mycobacterial alkaloids, cyclic 3-alkyl pyridinium dimers, from the Indonesian marine sponge Haliclona sp.
    Bioorg Med Chem Lett 2017 Aug 23;27(15):3503-3506. Epub 2017 May 23.
    Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
    Three new dimeric 3-alkyl pyridinium alkaloids, named haliclocyclamines A-C (1-3), were isolated together with five known congeners, cyclostellettamines A (4), B (5), C (6), E (7), and F (8), from the Indonesian marine sponge Haliclona sp. The structures of 1-3 were assigned based on their spectroscopic data (1D and 2D NMR, HRFABMS, ESIMS/MS, UV, and IR). Compounds 1-8 exhibited antimicrobial activities against Mycobacterium smegmatis with inhibition zones of 17, 10, 13, 14, 8, 8, 12, and 12mm, respectively, at 10μg/disc. Read More

    ZMPSTE24 Is Downstream Effector of Interferon-Induced Transmembrane Antiviral Activity.
    DNA Cell Biol 2017 Jul 8;36(7):513-517. Epub 2017 Jun 8.
    2 Department of Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts.
    The zinc metalloprotease ZMPSTE24 is a constitutively and ubiquitously expressed host restriction factor that is responsible for limiting infection by a broad spectrum of enveloped viruses, including influenza A, vesicular stomatitis, zika, ebola, Sindbis, cowpox, and vaccinia viruses, but not murine leukemia or adenovirus. Antiviral function is independent of ZMPSTE24 enzymatic activity. Protein interaction and genetic complementation studies indicate that ZMPSTE24 is a component of a common antiviral pathway that is associated with interferon-induced transmembrane proteins. Read More

    Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery.
    Front Oncol 2017 23;7:96. Epub 2017 May 23.
    Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
    Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly via cell lysis, while leaving non-cancerous tissues unharmed. Read More

    Novel Nonreplicating Vaccinia Virus Vector Enhances Expression of Heterologous Genes and Suppresses Synthesis of Endogenous Viral Proteins.
    MBio 2017 Jun 6;8(3). Epub 2017 Jun 6.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Viruses are used as expression vectors for protein synthesis, immunology research, vaccines, and therapeutics. Advantages of poxvirus vectors include the accommodation of large amounts of heterologous DNA, the presence of a cytoplasmic site of transcription, and high expression levels. On the other hand, competition of approximately 200 viral genes with the target gene for expression and immune recognition may be disadvantageous. Read More

    Duration of neutralizing antibody persisting in Thai individuals after childhood vaccination against smallpox.
    Asian Pac J Allergy Immunol 2017 Jun 1. Epub 2017 Jun 1.
    Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
    Background: Although smallpox was completely eliminated by 1980, it remains possible that variola virus could be intentionally released in an act of bioterrorism. Thus, several studies have been performed to detect antibody levels after smallpox vaccination of the current population in various countries to indicate the duration of maintenance of immunological memory. Our study endeavored to investigate the level of neutralizing (Nt) antibody responses of Thai individuals who had been immunized with smallpox vaccine during childhood. Read More

    Correlative super-resolution fluorescence and electron microscopy using conventional fluorescent proteins in vacuo.
    J Struct Biol 2017 Aug 30;199(2):120-131. Epub 2017 May 30.
    Electron Microscopy STP, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:
    Super-resolution light microscopy, correlative light and electron microscopy, and volume electron microscopy are revolutionising the way in which biological samples are examined and understood. Here, we combine these approaches to deliver super-accurate correlation of fluorescent proteins to cellular structures. We show that YFP and GFP have enhanced blinking properties when embedded in acrylic resin and imaged under partial vacuum, enabling in vacuo single molecule localisation microscopy. Read More

    Characterization of DNA Binding by the Isolated N-Terminal Domain of Vaccinia Virus DNA Topoisomerase IB.
    Biochemistry 2017 Jul 19;56(26):3307-3317. Epub 2017 Jun 19.
    Department of Chemistry and Biochemistry, The City College of New York , New York, New York 10031, United States.
    Vaccinia TopIB (vTopIB), a 314-amino acid eukaryal-type IB topoisomerase, recognizes and transesterifies at the DNA sequence 5'-(T/C)CCTT↓, leading to the formation of a covalent DNA-(3'-phosphotyrosyl(274))-enzyme intermediate in the supercoil relaxation reaction. The C-terminal segment of vTopIB (amino acids 81-314), which engages the DNA minor groove at the scissile phosphodiester, comprises an autonomous catalytic domain that retains cleavage specificity, albeit with a cleavage site affinity lower than that of the full-length enzyme. The N-terminal domain (amino acids 1-80) engages the major groove on the DNA face opposite the scissile phosphodiester. Read More

    Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma.
    Int J Cancer 2017 Sep 21;141(6):1257-1264. Epub 2017 Jun 21.
    Centre for Innovative Cancer research, Ottawa Hospital Research Institute, Ottawa, ON, KlH 8L6, Canada.
    The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Read More

    Glycosaminoglycans-Specific Cell Targeting and Imaging Using Fluorescent Nanodiamonds Coated with Viral Envelope Proteins.
    Anal Chem 2017 Jun 8;89(12):6527-6534. Epub 2017 Jun 8.
    Institute of Atomic and Molecular Sciences, Academia Sinica , Taipei 106, Taiwan.
    Understanding virus-host interactions is crucial for vaccine development. This study investigates such interactions using fluorescent nanodiamonds (FNDs) coated with vaccinia envelope proteins as the model system. To achieve this goal, we noncovalently conjugated 100 nm FNDs with rA27(aa 21-84), a recombinant envelope protein of vaccinia virus, for glycosaminoglycans (GAGs)-specific targeting and imaging of living cells. Read More

    5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy.
    Oncotarget 2017 May 7. Epub 2017 May 7.
    The Jenner Institute, University of Oxford, Roosevelt Drive Oxford, OX3 7DQ, United Kingdom.
    The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Read More

    Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects.
    J Int AIDS Soc 2017 05;20(1):1-11
    Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
    Introduction: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA).

    Methods: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA. Read More

    Recombinant Poxvirus and the Tumor Microenvironment: Oncolysis, Immune Regulation and Immunization.
    Biomedicines 2016 Aug 12;4(3). Epub 2016 Aug 12.
    Rutgers Cancer Institute of New Jersey, Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903-2681, USA.
    Oncolytic viruses (OVs) are being extensively studied for their potential roles in the development of cancer therapy regimens. In addition to their direct lytic effects, OVs can initiate and drive systemic antitumor immunity indirectly via release of tumor antigen, as well as by encoding and delivering immunostimulatory molecules. This combination makes them an effective platform for the development of immunotherapeutic strategies beyond their primary lytic function. Read More

    Immune Checkpoint Blockade, Immunogenic Chemotherapy or IFN-α Blockade Boost the Local and Abscopal Effects of Oncolytic Virotherapy.
    Cancer Res 2017 May 23. Epub 2017 May 23.
    Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France.
    Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VVWR-TK(-)RR(-)-Fcu1 can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8(+) T cells, and immune cell infiltrate in the tumor could be reprogrammed toward a higher ratio of effector T cells to regulatory CD4(+) T cells. Read More

    Bovine vaccinia: Inactivated Vaccinia virus vaccine induces protection in murine model.
    Vet Microbiol 2017 May 9;204:84-89. Epub 2017 Mar 9.
    Laboratório de Pesquisa em Virologia Animal, Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais - UFMG, Brazil. Electronic address:
    Bovine vaccinia (BV), caused by Vaccinia virus (VACV), is a zoonosis characterized by exanthematous lesions on the teats of dairy cows and the milkers' hands. Since 1999, due to the occurrence of many BV outbreaks in dairy farms across all Brazilian regions, there is a need to improve the control and prevention measures of the disease. Vaccination is one of the major tools to prevent viral diseases, and it could be an alternative for BV prevention. Read More

    Viral exploitation of the MEK/ERK pathway - A tale of vaccinia virus and other viruses.
    Virology 2017 Jul;507:267-275
    Signal Transduction Group/Viruses Laboratory, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, CEP: 31.270-901, Belo Horizonte, Minas Gerais, Brazil. Electronic address:
    The VACV replication cycle is remarkable in the sense that it is performed entirely in the cytoplasmic compartment of vertebrate cells, due to its capability to encode enzymes required either for regulating the macromolecular precursor pool or the biosynthetic processes. Although remarkable, this gene repertoire is not sufficient to confer the status of a free-living microorganism to the virus, and, consequently, the virus relies heavily on the host to successfully generate its progeny. During the complex virus-host interaction, viruses must deal not only with the host pathways to accomplish their temporal demands but also with pathways that counteract viral infection, including the inflammatory, innate and acquired immune responses. Read More

    Vaccinia virus G1 protein: absence of autocatalytic self-processing.
    Arch Virol 2017 May 18. Epub 2017 May 18.
    Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9/3, 1030, Vienna, Austria.
    Vaccinia virus relies on a series of proteolytic cleavage events involving two viral proteins, I7 and G1, to complete its life cycle. Furthermore, G1 itself is cleaved during vaccinia virus infection. However, convincing evidence is lacking to show whether G1 participates in autoproteolysis or is a substrate of another protease. Read More

    Serologic and Molecular Evidence of Vaccinia Virus Circulation among Small Mammals from Different Biomes, Brazil.
    Emerg Infect Dis 2017 Jun;23(6):931-938
    Vaccinia virus (VACV) is a zoonotic agent that causes a disease called bovine vaccinia, which is detected mainly in milking cattle and humans in close contact with these animals. Even though many aspects of VACV infection have been described, much is still unknown about its circulation in the environment and its natural hosts/reservoirs. To investigate the presence of Orthopoxvirus antibodies or VACV DNA, we captured small rodents and marsupials in 3 areas of Minas Gerais state, Brazil, and tested their samples in a laboratory. Read More

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