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    Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.
    J Vis Exp 2018 Apr 3(134). Epub 2018 Apr 3.
    Children's Hospital of Eastern Ontario (CHEO) Research Institute; Department of Biology, Microbiology and Immunology, University of Ottawa; Department of Pediatrics, University of Ottawa;
    High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. Read More

    Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?
    Cell Mol Life Sci 2018 Apr 20. Epub 2018 Apr 20.
    Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, 37007, Salamanca, Spain.
    DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). Read More

    The immunogenicity of recombinant vaccines based on Modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host.
    Antiviral Res 2018 Apr 17. Epub 2018 Apr 17.
    The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK. Electronic address:
    African horse sickness (AHS) is a lethal equine disease transmitted by Culicoides biting midges and caused by African horse sickness virus (AHSV). AHS is endemic to sub-Saharan Africa, but devastating outbreaks have been recorded periodically outside this region. The perceived risk of an AHS outbreak occurring in Europe has increased following the frequent epidemics caused in ruminants by bluetongue virus, closely related to AHSV. Read More

    Mutagenic repair of double-stranded DNA breaks in vaccinia virus genomes requires cellular DNA ligase IV activity in the cytosol.
    J Gen Virol 2018 Apr 20. Epub 2018 Apr 20.
    1​Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
    Poxviruses comprise a group of large dsDNA viruses that include members relevant to human and animal health, such as variola virus, monkeypox virus, cowpox virus and vaccinia virus (VACV). Poxviruses are remarkable for their unique replication cycle, which is restricted to the cytoplasm of infected cells. The independence from the host nucleus requires poxviruses to encode most of the enzymes involved in DNA replication, transcription and processing. Read More

    Manifold Roles of CCR7 and Its Ligands in the Induction and Maintenance of Bronchus-Associated Lymphoid Tissue.
    Cell Rep 2018 Apr;23(3):783-795
    Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Electronic address:
    The processes underlying the development and maintenance of tertiary lymphoid organs are incompletely understood. Using a Ccr7 knockout/knockin approach, we show that spontaneous bronchus-associated lymphoid tissue (BALT) formation can be caused by CCR7-mediated migration defects of dendritic cells (DCs) in the lung. Plt/plt mice that lack the CCR7 ligands CCL19 and CCL21-serine do not form BALT spontaneously because lung-expressed CCL21-leucine presumably suffices to maintain steady-state DC egress. Read More

    First-in-Human Randomized Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector.
    J Infect Dis 2018 Apr 13. Epub 2018 Apr 13.
    Harvard Medical School, Boston, MA.
    Background: Mosaic immunogens are bioinformatically engineered HIV-1 sequences designed to elicit clade independent coverage against globally circulating HIV-1 strains.

    Methods: This Phase 1 double-blind, randomized, placebo-controlled trial enrolled healthy HIV uninfected adults who received two doses of a modified vaccinia Ankara (MVA) vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naïve (N=15) and those who had received an HIV-1 vaccine four to six years earlier (Ad26. Read More

    Comparative sequence and structural analysis of Indian orf viruses based on major envelope immune-dominant protein (F1L), an homologue of pox viral p35/H3 protein.
    Gene 2018 Apr 12. Epub 2018 Apr 12.
    Pox Virus Laboratory, Division of Virology, ICAR-Indian Veterinary Research Institute, Mukteswar, 263138, Nainital (District), Uttarakhand, India.
    Orf virus (ORFV), a member of the genus Parapoxvirus in the family Poxviridae, is the cause of orf, a highly contagious zoonotic viral disease that affects mainly sheep and goats. In the present study, the sequence and phylogenetic analysis of Indian ORFV isolates (n = 15) from natural outbreaks in sheep and goats belonging to different geographical regions were analysed on the basis of F1L gene along with homology modelling of F1L protein. Multiple sequence alignments revealed highly conserved C-terminus and heterogeneity of N-terminus region of F1L among all orf viruses studied. Read More

    Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial.
    PLoS One 2018 13;13(4):e0195897. Epub 2018 Apr 13.
    Bavarian Nordic GmbH, Martinsried, Germany.
    Background: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.

    Methods: The trial was conducted at 34 sites in the US. Read More

    Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence.
    Nat Microbiol 2018 Apr 9. Epub 2018 Apr 9.
    Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
    To orchestrate context-dependent signalling programmes, poxviruses encode two dual-specificity enzymes, the F10 kinase and the H1 phosphatase. These signalling mediators are essential for poxvirus production, yet their substrate profiles and systems-level functions remain enigmatic. Using a phosphoproteomic screen of cells infected with wild-type, F10 and H1 mutant vaccinia viruses, we systematically defined the viral signalling network controlled by these enzymes. Read More

    Inhibition of vaccinia virus replication by nitazoxanide.
    Virology 2018 May 3;518:398-405. Epub 2018 Apr 3.
    Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Department of Microbiology, University of Washington, Seattle, WA 98115, United States; Department of Medicine, University of Washington, Seattle, WA 98115, United States. Electronic address:
    Nitazoxanide (NTZ) is an FDA-approved anti-protozoal drug that inhibits several bacteria and viruses as well. However, its effect on poxviruses is unknown. Therefore, we investigated the impact of NTZ on vaccinia virus (VACV). Read More

    Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth.
    Proc Natl Acad Sci U S A 2018 Apr 2;115(16):E3808-E3816. Epub 2018 Apr 2.
    Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden;
    The zinc finger CCCH-type containing 11A () gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Read More

    Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase.
    Sci Rep 2018 Mar 29;8(1):5364. Epub 2018 Mar 29.
    Laboratory of DNA Viruses, Center for Biologics Evaluations and Research, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
    Influenza subtypes such as H7 have pandemic potential since they are able to infect humans with severe consequences, as evidenced by the ongoing H7N9 infections in China that began in 2013. The diversity of H7 viruses calls for a broadly cross-protective vaccine for protection. We describe the construction of recombinant modified vaccinia virus Ankara (MVA) vectors expressing the hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both Eurasian and North American H7 lineages - A/mallard/Netherlands/12/2000 (H7N3), A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9). Read More

    A single vaccination with non-replicating MVA at birth induces both immediate and long-term protective immune responses.
    Vaccine 2018 Apr 27;36(18):2427-2434. Epub 2018 Mar 27.
    Bavarian Nordic GmbH, Fraunhoferstrasse 13, D-82152 Martinsried, Germany. Electronic address:
    Newborns are considered difficult to protect against infections shortly after birth, due to their ineffective immune system that shows quantitative and qualitative differences compared to adults. However, here we show that a single vaccination of mice at birth with a replication-deficient live vaccine Modified Vaccinia Ankara [MVA] efficiently induces antigen-specific B- and T-cells that fully protect against a lethal Ectromelia virus challenge. Protection was induced within 2 weeks and using genetically modified mice we show that this protection was mainly T-cell dependent. Read More

    Matrix-M™ adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice.
    Immunol Res 2018 Apr;66(2):224-233
    Novavax AB, Kungsgatan 109, SE-75318, Uppsala, Sweden.
    Influenza viruses continuously circulate in the human population and escape recognition by virus neutralizing antibodies induced by prior infection or vaccination through accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a vaccine that provides broad protection against different influenza A viruses are under investigation, including use of recombinant (r) viral vectors and adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a promising vaccine vector that efficiently induces B and T cell responses specific for the antigen of interest. Read More

    Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development.
    NPJ Vaccines 2018 20;3:11. Epub 2018 Mar 20.
    4Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX USA.
    Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family . It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Read More

    A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses.
    Nat Commun 2018 Mar 26;9(1):1230. Epub 2018 Mar 26.
    QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia.
    Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus mosquitoes. The "Sementis Copenhagen Vector" (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe a single-vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci. Read More

    Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination.
    Nat Commun 2018 Mar 23;9(1):1212. Epub 2018 Mar 23.
    U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, 20901, USA.
    Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Read More

    Myocarditis secondary to smallpox vaccination.
    BMJ Case Rep 2018 Mar 22;2018. Epub 2018 Mar 22.
    Cardiology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
    The development of vaccines ushered in the most profound advancement in 20th century medicine, and have widely been regarded as the one of the most important scientific discovery in the history of mankind. However, vaccines are not without risk; reactions can range from injection site reactions to life-threatening anaphylaxis. Among the more serious vaccine-related sequela is myocarditis. Read More

    Serological Evidence of Circulation Among Equids, Southeast Brazil.
    Front Microbiol 2018 8;9:402. Epub 2018 Mar 8.
    Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
    Since 1999 (VACV) outbreaks involving bovines and humans have been reported in Brazil; this zoonosis is known as Bovine Vaccinia (BV) and is mainly an occupational disease of milkers. It was only in 2008 (and then again in 2011 and 2014) however, that VACV was found causing natural infections in Brazilian equids. These reports involved only equids, no infected humans or bovines were identified, and the sources of infections remain unknown up to date. Read More

    The Host Factor Early Growth Response Gene (EGR-1) Regulates Vaccinia virus Infectivity during Infection of Starved Mouse Cells.
    Viruses 2018 03 21;10(4). Epub 2018 Mar 21.
    Grupo de Transdução de Sinal, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas, Brazil.
    Evolution has equipped poxvirus genomes with the coding capacity for several virus-host interaction products which interfere with host cell gene expression and protein function, creating an adequate intracellular environment for a productive infection. We show here that (VACV) induces the expression of the cellular transcription factor EGR-1 (early growth response-1) in Mouse Embryonic Fibroblasts (MEFs) through the MEK (mitogen-activated protein kinase (MAPK)/ERK)/ERK (extracellular signal-regulated kinases) pathway, from 3 to 12 h post infection (h.p. Read More

    Characterization of murine antibody responses to vaccinia virus envelope protein A14 reveals an immunodominant antigen lacking of effective neutralization targets.
    Virology 2018 May 17;518:284-292. Epub 2018 Mar 17.
    Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address:
    Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Read More

    Smallpox vaccine complications: the dermatologist's role in diagnosis and management.
    Cutis 2018 Feb;101(2):87-90
    University of Colorado Hospital, Aurora, USA.
    In 2002, the United States implemented a new program for smallpox vaccinations among military personnel using a live vaccinia virus product. Approximately 2.4 million US military service members and health care workers have since been inoculated, with considerable numbers experiencing adverse reactions. Read More

    Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence.
    Emerg Infect Dis 2018 Apr;24(4):646-653
    We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York's and 17% of Sydney's population are immunosuppressed. The highest smallpox infection rates were in persons 0-19 years of age, but the highest death rates were in those >45 years of age. Read More

    How Does Vaccinia Virus Interfere With Interferon?
    Adv Virus Res 2018 16;100:355-378. Epub 2018 Feb 16.
    University of Cambridge, Cambridge, United Kingdom.
    Interferons (IFNs) are secreted glycoproteins that are produced by cells in response to virus infection and other stimuli and induce an antiviral state in cells bearing IFN receptors. In this way, IFNs restrict virus replication and spread before an adaptive immune response is developed. Viruses are very sensitive to the effects of IFNs and consequently have evolved many strategies to interfere with interferon. Read More

    Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan.
    Antiviral Res 2018 May 14;153:49-59. Epub 2018 Mar 14.
    Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:
    The development of an effective HIV-1 vaccine is still a global priority. In recent years, vaccinia virus (VV) has been widely used as an HIV-1 vaccine vector, but its immune efficacy against HIV-1 antigens needs to be optimized. The extracellular enveloped virus (EEV) of VV is capable of faster entry, earlier release, and long-range dissemination. Read More

    Post-Smallpox Vaccination Skin Eruption in a Marine.
    Mil Med 2018 Mar 13. Epub 2018 Mar 13.
    Aerospace Medicine, Marine Air Group-24, 1st Marine Aircraft Wing, BOX 63047, MCBH Kaneohe Bay, HI 96863.
    This case report examines a vesiculopustular reaction which occurred in a young Marine 9 d after receiving the smallpox vaccination. Review of the CDC guidelines, ACAM2000 package insert, and literature surrounding the smallpox vaccine reveals several well-established adverse cutaneous reactions associated with vaccination. These dermatologic reactions are typically mild and self-limited, but do have the potential to be life threatening - especially in those with immunocompromise. Read More

    Full Genome Sequence of the Western Reserve Strain of Vaccinia Virus Determined by Third-Generation Sequencing.
    Genome Announc 2018 Mar 15;6(11). Epub 2018 Mar 15.
    Department of Medical Biology, Faculty of Medicine, University of Szeged, Szeged, Hungary
    The vaccinia virus is a large, complex virus belonging to the family. Here, we report the complete, annotated genome sequence of the neurovirulent Western Reserve laboratory strain of this virus, which was sequenced on the Pacific Biosciences RS II and Oxford Nanopore MinION platforms. Read More

    Vaccinia virus phospholipase protein F13 promotes the rapid entry of extracellular virions into cells.
    J Virol 2018 Mar 14. Epub 2018 Mar 14.
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
    The vaccinia virus protein F13, encoded by the F13L gene, is conserved across the subfamily and is critical among orthopoxviruses to produce the wrapped form of virus that is required for cell-to-cell spread. F13 is the major envelope protein on the membrane of extracellular forms of virus, however it is not known if F13 is required in steps post-wrapping. In this report, we utilize two temperature-sensitive vaccinia virus mutants from the Condit collection of temperature-sensitive viruses whose small plaque phenotypes have been mapped to the F13L gene. Read More

    The use of the vaccinia virus complement control protein (VCP) in the rat retina.
    PLoS One 2018 13;13(3):e0193740. Epub 2018 Mar 13.
    The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
    The complement system is highly implicated in both the prevalence and progression of Age-Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown to be effective as a complement inhibitor in neuroinflammatory models including traumatic brain injury and spinal cord injury. Read More

    Characterization of the immune response elicited by the vaccinia virus L3 protein delivered as naked DNA.
    Vaccine 2018 04 7;36(15):2049-2055. Epub 2018 Mar 7.
    Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA. Electronic address:
    Poxviruses are complex dsDNA viruses with over 200 genes, many of them with unknown role in the stimulation of immune responses. Among these, the vaccinia virus (VACV) L3L ORF encodes an essential protein for the transcription of the VACV early genes. To the best of our knowledge, the immune response elicited by L3 has not been characterized. Read More

    Bovine Vaccinia: Insights into the Disease in Cattle.
    Viruses 2018 03 9;10(3). Epub 2018 Mar 9.
    Laboratório de Pesquisa em Virologia Animal, Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
    Bovine vaccinia (BV), caused by (VACV), is a zoonosis characterized by exanthematous lesions in the teats of dairy cows and the hands of milkers and is an important public health issue. Severe VACV-induced lesions in the teats and udder of cows and buffaloes could lead to mastitis and other secondary infections, thereby reducing productivity and resulting in economic losses to the dairy industry. In Brazil, BV re-emerged in the late 1990s and is now endemic in most of the Brazilian territory. Read More

    Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.
    EBioMedicine 2018 Mar 15;29:146-154. Epub 2018 Feb 15.
    The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address:
    Background: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). Read More

    Distinct Immunogenicity and Efficacy of Poxvirus-based Vaccine Candidates against Ebola Virus expressing GP and VP40 Proteins.
    J Virol 2018 Mar 7. Epub 2018 Mar 7.
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
    and species cause a severe disease in humans and non-human primates (NHPs) characterized by high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013-2016 outbreak in West Africa highlighted the need of EVD-specific medical countermeasures. Here, we have generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA), expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs). Read More

    Loss of Actin-Based Motility Impairs Ectromelia Virus Release In Vitro but Is Not Critical to Spread In Vivo.
    Viruses 2018 03 5;10(3). Epub 2018 Mar 5.
    School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
    Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. Read More

    The Host Restriction Factor Interferon-Inducible Transmembrane Protein 3 Inhibits Vaccinia Virus Infection.
    Front Immunol 2018 16;9:228. Epub 2018 Feb 16.
    State Key Laboratory of Proteomics, Beijing Proteome Research Center, Institute of Radiation Medicine, Beijing, China.
    Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Read More

    Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory.
    Viruses 2018 02 28;10(3). Epub 2018 Feb 28.
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
    The increasing frequency of monkeypox virus infections, new outbreaks of other zoonotic orthopoxviruses and concern about the re-emergence of smallpox have prompted research into developing antiviral drugs and better vaccines against these viruses. This article considers the genetic engineering of vaccinia virus (VACV) to enhance vaccine immunogenicity and safety. The virulence, immunogenicity and protective efficacy of VACV strains engineered to lack specific immunomodulatory or host range proteins are described. Read More

    Virulent poxviruses inhibit DNA sensing by preventing STING activation.
    J Virol 2018 Feb 28. Epub 2018 Feb 28.
    Department of Microbial Sciences, University of Surrey, Guildford, United Kingdom
    Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Read More

    Construction and characterization of bacterial artificial chromosomes harboring the full-length genome of a highly attenuated vaccinia virus LC16m8.
    PLoS One 2018 23;13(2):e0192725. Epub 2018 Feb 23.
    Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.
    LC16m8 (m8), a highly attenuated vaccinia virus (VAC) strain, was developed as a smallpox vaccine, and its safety and immunogenicity have been confirmed. Here, we aimed to develop a system that recovers infectious m8 from a bacterial artificial chromosome (BAC) that retains the full-length viral genomic DNA (m8-BAC system). The infectious virus was successfully recovered from a VAC-BAC plasmid, named pLC16m8-BAC. Read More

    Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer.
    PLoS One 2018 23;13(2):e0193131. Epub 2018 Feb 23.
    Department of Microbiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States of America.
    Pancreatic cancer is the 5th leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. Read More

    Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP.
    Sci Rep 2018 Feb 21;8(1):3390. Epub 2018 Feb 21.
    The Jenner Institute, University of Oxford, Oxford, UK.
    Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. Read More

    A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates.
    PLoS One 2018 20;13(2):e0192312. Epub 2018 Feb 20.
    Janssen Vaccines & Prevention B.V., Leiden, Netherlands.
    The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV). Read More

    Prime and Boost Vaccination Elicit a Distinct Innate Myeloid Cell Immune Response.
    Sci Rep 2018 Feb 15;8(1):3087. Epub 2018 Feb 15.
    CEA - Université Paris Sud 11 - INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT department, IBFJ, 92265, Fontenay-aux-Roses, France.
    Understanding the innate immune response to vaccination is critical in vaccine design. Here, we studied blood innate myeloid cells after first and second immunization of cynomolgus macaques with the modified vaccinia virus Ankara. The inflammation at the injection site was moderate and resolved faster after the boost. Read More

    A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection.
    PLoS Pathog 2018 Feb 15;14(2):e1006884. Epub 2018 Feb 15.
    Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
    Host restriction factors constitute a formidable barrier for viral replication to which many viruses have evolved counter-measures. Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. A paralog of SAMD9, SAMD9L, is also encoded by some mammals, while only one of two paralogs is retained by others. Read More

    Bayesian reconstruction of the evolutionary history and cross-species transition of variola virus and orthopoxviruses.
    J Med Virol 2018 Jun 12;90(6):1134-1141. Epub 2018 Mar 12.
    Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy.
    Variola virus (VARV), the causative agent of smallpox, is an exclusively human virus belonging to the genus Orthopoxvirus, which includes many other viral species covering a wide range of mammal hosts, such as vaccinia, cowpox, camelpox, taterapox, ectromelia, and monkeypox virus. The tempo and mode of evolution of Orthopoxviruses were reconstructed using a Bayesian phylodynamic framework by analysing 80 hemagglutinin sequences retrieved from public databases. Bayesian phylogeography was used to estimate their putative ancestral hosts. Read More

    New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy.
    Biologics 2018 9;12:43-60. Epub 2018 Feb 9.
    PanTherapeutics, Lutry, Switzerland.
    Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses - adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses - have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Read More

    Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist of the Type I Interferon-Induced Antiviral State.
    J Virol 2018 May 13;92(9). Epub 2018 Apr 13.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Type I interferons (IFNs) induce expression of more than 300 cellular genes that provide protection against viruses and other pathogens. For survival, viruses evolved defenses to prevent the IFN response or counteract the IFN-induced antiviral state. However, because viruses and cells coevolved, the dynamic relationship between virus and host is difficult to discern. Read More

    Virus-Like-Vaccines against HIV.
    Vaccines (Basel) 2018 Feb 11;6(1). Epub 2018 Feb 11.
    Department of Immunology and Microbiology (ISIM), Faculty of Health Sciences, University of Copenhagen, The Panum Institute Building 7-13-16, Blegdamsvej 3B, DK2200 Copenhagen, Denmark.
    Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Read More

    Superinfection Exclusion between Two High-Risk Human Papillomavirus (HPV) Types During a Co-Infection.
    J Virol 2018 Feb 7. Epub 2018 Feb 7.
    Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania, The United States of America.
    Superinfection exclusion is a common phenomenon whereby a single cell is unable to be infected by two types of the same pathogen. Superinfection exclusion has been described for various viruses including vaccinia virus, measles virus, hepatitis C virus, influenza A virus, and human immunodeficiency virus. Additionally, the mechanism of exclusion has been observed at various steps in the viral life cycle including attachment, entry, viral genomic replication, transcription, and exocytosis. Read More

    High-cell-density cultivations to increase MVA virus production.
    Vaccine 2018 Feb 9. Epub 2018 Feb 9.
    Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106 Magdeburg, Germany; Chair for Bioprocess Engineering, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany.
    Increasing the yield and the productivity in cell culture-based vaccine manufacturing using high-cell-density (HCD) cultivations faces a number of challenges. For example, medium consumption should be low to obtain a very high concentration of viable host cells in an economical way but must be balanced against the requirement that accumulation of toxic metabolites and limitation of nutrients have to be avoided. HCD cultivations should also be optimized to avoid unwanted induction of apoptosis or autophagy during the early phase of virus infection. Read More

    In vitro susceptibility to ST-246 and Cidofovir corroborates the phylogenetic separation of Brazilian Vaccinia virus into two clades.
    Antiviral Res 2018 Apr 7;152:36-44. Epub 2018 Feb 7.
    Laboratório de Microbiologia Clínica, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, CEP 31270-901, Belo Horizonte, Brazil. Electronic address:
    The Orthopoxvirus (OPV) genus of the Poxviridae family contains several human pathogens, including Vaccinia virus (VACV), which have been implicating in outbreaks of a zoonotic disease called Bovine Vaccinia in Brazil. So far, no approved treatment exists for OPV infections, but ST-246 and Cidofovir (CDV) are now in clinical development. Therefore, the objective of this work was to evaluate the susceptibility of five strains of Brazilian VACV (Br-VACV) to ST-246 and Cidofovir. Read More

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