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    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 Nov 11. 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 2017 Nov 9. Epub 2017 Nov 9.
    LJI, United States;
    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 Nov 7. Epub 2017 Nov 7.
    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

    Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions.
    JCI Insight 2017 Nov 2;2(21). Epub 2017 Nov 2.
    The Jenner Institute, University of Oxford, Oxford, United Kingdom.
    The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. Read More

    Isolation and Characterization of vΔI3 Confirms that the Vaccinia Virus SSB Plays an Essential Role in Viral Replication.
    J Virol 2017 Nov 1. Epub 2017 Nov 1.
    Departments of Biochemistry & Molecular Biology and Microbiology & Immunology, Medical University of South Carolina
    Vaccinia virus is unusual among DNA viruses in replicating exclusively in the cytoplasm of infected cells. The ssDNA binding protein (SSB), I3, is among the replication machinery encoded by the 195 kb genome, although direct genetic analysis of I3 has been lacking. Herein, we describe a complementing cell line (CV1-I3) that fully supports the replication of a null virus lacking the I3 ORF (vΔI3). Read More

    Enhanced immunotherapy by combining a vaccine with a novel murine GITR ligand fusion protein.
    Oncotarget 2017 Sep 7;8(43):73469-73482. Epub 2017 Sep 7.
    Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    Immunotherapy was significantly enhanced in a murine tumor model by combining a vaccine with a fusion protein designed to target the glucocorticoid-induced tumor necrosis factor (TNF) receptor related gene (GITR) on the surface of T cells. The recombinant poxvirus-based vaccine platform included Modified Vaccinia virus Ankara (rMVA) and fowlpox (rF) vectors as the driver immunogens both engineered to express the human carcinoembryonic antigen (CEA) and three murine costimulatory molecules B7.1, ICAM-1, LFA-3 (designated TRICOM). Read More

    Rapid Generation of Multiple Loci-Engineered Marker-free Poxvirus and Characterization of a Clinical-Grade Oncolytic Vaccinia Virus.
    Mol Ther Methods Clin Dev 2017 Dec 30;7:112-122. Epub 2017 Sep 30.
    UPMC Hillman Cancer Center and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
    Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic) selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. Read More

    Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein.
    PLoS Negl Trop Dis 2017 Oct 30;11(10):e0006036. Epub 2017 Oct 30.
    Unidad de Procesamiento Antigénico, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
    Background: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. Read More

    Activation and trafficking of CD8(+) T cells during viral skin infection: immunological lessons learned from vaccinia virus.
    Curr Opin Virol 2017 Oct 24;28:12-19. Epub 2017 Oct 24.
    Departments of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, United States; Departments of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, United States; Departments of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, United States. Electronic address:
    Epicutaneous delivery of vaccinia virus (VacV) by scarification of the skin generates robust and durable protective immunity, which was ultimately responsible for eradicating smallpox from the human race. Therefore, infection of the skin with VacV is often used in experimental model systems to study the activation of adaptive immunity, as well as the development and functional features of immunological memory. Here, we describe recent advances using this viral infection to identify and characterize the mechanisms regulating the activation and trafficking of cytotoxic CD8(+) T cells into the inflamed skin, the migratory features of CD8(+) T cells within the skin microenvironment, and finally, their subsequent differentiation into tissue-resident memory cells. Read More

    ISG15 governs mitochondrial function in macrophages following vaccinia virus infection.
    PLoS Pathog 2017 Oct 27;13(10):e1006651. Epub 2017 Oct 27.
    Department of Preventive Medicine, Public Health and Microbiology, Universidad Autónoma, Madrid, Spain.
    The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS) were pathways altered in ISG15-/- BMDM treated with IFN. Read More

    Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3.
    Proc Natl Acad Sci U S A 2017 Oct 9;114(43):11506-11511. Epub 2017 Oct 9.
    Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287;
    Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Read More

    Inertial picobalance reveals fast mass fluctuations in mammalian cells.
    Nature 2017 Oct;550(7677):500-505
    Eidgenössische Technische Hochschule (ETH) Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
    The regulation of size, volume and mass in living cells is physiologically important, and dysregulation of these parameters gives rise to many diseases. Cell mass is largely determined by the amount of water, proteins, lipids, carbohydrates and nucleic acids present in a cell, and is tightly linked to metabolism, proliferation and gene expression. Technologies have emerged in recent years that make it possible to track the masses of single suspended cells and adherent cells. Read More

    Evolutionary cancer-favoring engineered vaccinia virus for metastatic hepatocellular carcinoma.
    Oncotarget 2017 Sep 20;8(42):71489-71499. Epub 2017 Apr 20.
    Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Busan 602-739, Republic of Korea.
    Engineered vaccinia virus-based therapy shows promising results in patients with advanced hepatocellular carcinoma, although a strategic virus design for the metastatic liver and the study of its efficacy in treating the cancer has not been well assessed. In this paper, we proposed a simple and strategic virus design for targeting metastatic hepatocellular carcinoma. We developed an evolutionary cancer-favoring engineered vaccinia virus (CVV, which is produced by repeated selective replication in cancerous tissues and then deleting viral thymidine kinase genes) and investigated its therapeutic effects on metastatic liver cancer. Read More

    Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization.
    PLoS One 2017 24;12(10):e0186602. Epub 2017 Oct 24.
    Immunopathology and Cellular Immunology, AIDS Research Group, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
    Background: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost.

    Methods: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. Read More

    Vaccinia virus protein A49 activates Wnt signalling by targetting the E3 ligase β-TrCP.
    J Gen Virol 2017 Oct 17. Epub 2017 Oct 17.
    Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP, Cambridge, UK.
    Vaccinia virus (VACV) encodes multiple proteins inhibiting the NF-κB signalling pathway. One of these, A49, targets the E3 ubiquitin ligase β-TrCP, which is responsible for the ubiquitylation and consequential proteosomal degradation of IκBα and the release of the NF-κB heterodimer. β-TrCP is a pleiotropic enzyme ubiquitylating multiple cellular substrates, including the transcriptional activator β-catenin. Read More

    VRK1 promotes cisplatin resistance by up-regulating c-MYC via c-Jun activation and serves as a therapeutic target in esophageal squamous cell carcinoma.
    Oncotarget 2017 Sep 7;8(39):65642-65658. Epub 2017 Aug 7.
    Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
    Esophageal squamous cell carcinoma (ESCC) is a common malignant disease characterized by poor prognosis. Chemoresistance remains a major cause of ESCC relapse. Vaccinia-related kinase 1 (VRK1) has previously been identified as a cancer-related gene. Read More

    Retrospective proteomic analysis of serum after Akhmeta virus infection: new suspect case identification and insights into poxvirus humoral immunity.
    J Infect Dis 2017 Oct 6. Epub 2017 Oct 6.
    Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
    Serologic cross-reactivity, a hallmark of orthopoxvirus (OPXV) infection, makes species-specific diagnosis of infection difficult. In this study, we used a Variola virus (VARV) proteome microarray to characterize and differentiate antibody responses to non-vaccinia OPXV infections from smallpox vaccination. The profile of two-case patients infected with newly discovered OPXV, Akhmeta virus (AKMV), exhibited antibody responses of greater intensity and broader recognition of viral proteins and includes the B21/22 family glycoproteins not encoded by vaccinia virus (VACV) strains used as vaccines. Read More

    Hypothesis: RNA and DNA Viral Sequence Integration into the Mammalian Host Genome Supports Long-Term B Cell and T Cell Adaptive Immunity.
    Viral Immunol 2017 Nov 13;30(9):628-632. Epub 2017 Oct 13.
    6 Trudeau Institute , Saranac Lake, New York.
    Viral sequence integration into the mammalian genome has long been perceived as a health risk. In some cases, integration translates to chronic viral infection, and in other instances, oncogenic gene mutations occur. However, research also shows that animal cells can benefit from integrated viral sequences (e. Read More

    HIV-1 gp120 Protein and MVAgp140 Boost Immunogens Increase immunogenicity of a DNA/MVA HIV-1 Vaccine.
    J Virol 2017 Oct 11. Epub 2017 Oct 11.
    GeoVax, Inc., Smyrna, GA 30080
    An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia Ankara (MVA) expressing HIV-1 Env on virus like particles. Here we evaluated whether the addition of a gp120 protein in alum or MVA expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime - MVA boost vaccine. Read More

    Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner.
    PLoS One 2017 11;12(10):e0185786. Epub 2017 Oct 11.
    Immunology and Infectious Disease Unit, GIGA-I3, University of Liège, Liège, Belgium.
    Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel outgrowth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Read More

    HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
    PLoS One 2017 11;12(10):e0177863. Epub 2017 Oct 11.
    GeoVax Inc., Smyrna, GA, United States of America.
    Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Read More

    Targeting Nucleotide Biosynthesis: A Strategy for Improving the Oncolytic Potential of DNA Viruses.
    Front Oncol 2017 26;7:229. Epub 2017 Sep 26.
    Faculty of Medicine and Dentistry, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
    The rapid growth of tumors depends upon elevated levels of dNTPs, and while dNTP concentrations are tightly regulated in normal cells, this control is often lost in transformed cells. This feature of cancer cells has been used to advantage to develop oncolytic DNA viruses. DNA viruses employ many different mechanisms to increase dNTP levels in infected cells, because the low concentration of dNTPs found in non-cycling cells can inhibit virus replication. Read More

    Exploiting 2A peptides to elicit potent neutralizing antibodies by a multi-subunit herpesvirus glycoprotein complex.
    J Virol Methods 2018 Jan 6;251:30-37. Epub 2017 Oct 6.
    Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA, USA. Electronic address:
    Neutralizing antibodies (NAb) interfering with glycoprotein complex-mediated virus entry into host cells are thought to contribute to the protection against herpesvirus infection. However, using herpesvirus glycoprotein complexes as vaccine antigens can be complicated by the necessity of expressing multiple subunits simultaneously to allow efficient complex assembly and formation of conformational NAb epitopes. By using a novel bacterial artificial chromosome (BAC) clone of the clinically deployable Modified Vaccinia Ankara (MVA) vector and exploiting ribosomal skipping mediated by 2A peptides, MVA vectors were generated that expressed self-processing subunits of the human cytomegalovirus (HCMV) pentamer complex (PC) composed of gH, gL, UL128, UL130, and UL131A. Read More

    The development of a monolith-based purification process for Orthopoxvirus vaccinia virus Lister strain.
    J Chromatogr A 2017 Nov 5;1524:87-100. Epub 2017 Sep 5.
    Department of Biochemical Engineering, University College London, UK. Electronic address:
    The purification of large viruses remains an important field of research and development. The development of efficient purification trains is restricted by limited analytical methods, as well as by the complexity of large viruses, as well as the high variability in starting material from cell culture. Vaccinia virus holds great potential as an oncolytic and immunotherapeutic vaccine against a broad spectrum of cancers. Read More

    Strategies to obtain multiple recombinant modified vaccinia Ankara vectors. Applications to influenza vaccines.
    J Virol Methods 2018 Jan 4;251:7-14. Epub 2017 Oct 4.
    Molecular Immunology Unit, San Raffaele Research Institute, Via Olgettina 58, 20132, Milan, Italy. Electronic address:
    As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI. Read More

    A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity.
    Methods Mol Biol 2018 ;1604:157-167
    Montana Biotechnology Center, University of Montana, Science Complex Room 221, Missoula, MT, 59812, USA.
    For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. Read More

    Identifying host factors associated with DNA replicated during virus infection.
    Mol Cell Proteomics 2017 Oct 2. Epub 2017 Oct 2.
    Children's Hospital of Philadelphia, United States;
    Viral DNA genomes replicating in cells encounter a myriad of host factors that facilitate or hinder viral replication. Viral proteins expressed early during infection modulate host factors interacting with viral genomes, recruiting proteins to promote viral replication, and limiting access to antiviral repressors. Although some host factors manipulated by viruses have been identified, we have limited knowledge of pathways exploited during infection and how these differ between viruses. Read More

    Intradermal HIV-1 DNA immunization using needle-free ZetajetTM injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and immunogenic in Mozambican young adults: a phase I randomized controlled trial.
    AIDS Res Hum Retroviruses 2017 Oct 2. Epub 2017 Oct 2.
    Karolinska Institutet, Department of Education and Clinical Research, Stockholm, Sweden ;
    We assessed safety and immunogenicity of HIV-DNA priming using ZetajetTM, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0. Read More

    Safety and Immunogenicity of PENNVAX®-G DNA Prime Administered by Biojector® 2000 or CELLECTRA® Electroporation Device with Modified Vaccinia Ankara-CMDR Boost.
    J Infect Dis 2017 Sep 2. Epub 2017 Sep 2.
    US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States.
    Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX®-G DNA/ MVA-CMDR prime-boost HIV vaccine, with intramuscular DNA delivery by either Biojector® 2000 needle free injection system (Biojector) or by CELLECTRA® electroporation device.

    Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg PENNVAX®-G DNA delivered IM by Biojector or electroporation at baseline and week 4 followed by IM injection of 108 pfu MVA-CMDR at week 12 and 24. The open label Part A was conducted in the US, followed by a double-blind, placebo controlled Part B in East Africa. Read More

    Selective recruitment of nucleoporins on vaccinia virus factories and the role of Nup358 in viral infection.
    Virology 2017 Dec 28;512:151-160. Epub 2017 Sep 28.
    National Centre for Cell Science, S.P. Pune University Campus, Ganeshkhind, Pune 411007, India. Electronic address:
    Vaccinia virus (VACV), a member of the Poxviridae family, uses cytoplasmic factories for its replication. Recent studies indicated that VACV infection requires a set of nucleoporins. However, how the nucleoporins contribute to viral life cycle remains unclear. Read More

    Functional insights into pathogen biology from 3D electron microscopy.
    FEMS Microbiol Rev 2017 Nov;41(6):828-853
    Max Planck Institute of Biophysics, Max-von-Laue Strasse 3, 60438 Frankfurt, Germany.
    In recent years, novel imaging approaches revolutionised our understanding of the cellular and molecular biology of microorganisms. These include advances in fluorescent probes, dynamic live cell imaging, superresolution light and electron microscopy. Currently, a major transition in the experimental approach shifts electron microscopy studies from a complementary technique to a method of choice for structural and functional analysis. Read More

    In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging.
    Virulence 2017 Sep 29. Epub 2017 Sep 29.
    a Wellman Center for Photomedicine , Massachusetts General Hospital , Boston , MA , USA.
    Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative. Dedicated bioluminescence imaging (BLI) cameras can record the light emitted from living animals in real time allowing non-invasive, longitudinal monitoring of the anatomical location and growth of infectious microorganisms as measured by strength of the BLI signal. Read More

    Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection.
    Cell Rep 2017 Sep;20(13):3176-3187
    Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address:
    Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to lymphoid organs, virus applied to skin by scarification does not spread to draining lymph nodes. Using cutaneous infection by scarification, we analyzed the effect of viral infection on lymphatic transport and evaluated its role at the host-pathogen interface. Read More

    Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells.
    Biomed Res Int 2017 30;2017:3620510. Epub 2017 Aug 30.
    Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.
    Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. Read More

    Construction & establishment of two minigenome rescue systems for Chandipura virus driven by recombinant vaccinia virus expressing T7 polymerase.
    Indian J Med Res 2017 May;145(5):651-658
    Department of Biotechnology, University of Calcutta, Kolkata, India.
    Background & Objectives: Chandipura virus (CHPV) is an emerging pathogenic rhabdovirus with a high case fatality rate. There are no reports of a minigenome system for CHPV, which could help its study without having to use the infectious agent. This study was, therefore, undertaken for the establishment of T7 polymerase-driven minigenome system for CHPV. Read More

    Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues.
    Cell 2017 Oct 21;171(2):398-413.e21. Epub 2017 Sep 21.
    Faculty of Arts & Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address:
    A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. Read More

    Safety and immunogenicity of heterologous prime-boost immunization with viral-vectored malaria vaccines adjuvanted with Matrix-M™.
    Vaccine 2017 Oct 21;35(45):6208-6217. Epub 2017 Sep 21.
    Jenner Institute, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7DQ, UK.
    The use of viral vectors in heterologous prime-boost regimens to induce potent T cell responses in addition to humoral immunity is a promising vaccination strategy in the fight against malaria. We conducted an open-label, first-in-human, controlled Phase I study evaluating the safety and immunogenicity of Matrix-M adjuvanted vaccination with a chimpanzee adenovirus serotype 63 (ChAd63) prime followed by a modified vaccinia Ankara (MVA) boost eight weeks later, both encoding the malaria ME-TRAP antigenic sequence (a multiple epitope string fused to thrombospondin-related adhesion protein). Twenty-two healthy adults were vaccinated intramuscularly with either ChAd63-MVA ME-TRAP alone (n=6) or adjuvanted with 25μg (n=8) or 50μg (n=8) Matrix-M. Read More

    PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8(+) T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination.
    J Immunol 2017 Nov 22;199(9):3348-3359. Epub 2017 Sep 22.
    Department of Microbiology and Immunology, Western University, London, Ontario N6A 5C1, Canada;
    The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. Read More

    Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG(®)): a global review.
    Vet Res 2017 Sep 22;48(1):57. Epub 2017 Sep 22.
    LandCow Consulting, P.O. Box 5651, Madison, WI, 53705, USA.
    RABORAL V-RG(®) is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Read More

    Tagging of the vaccinia virus protein F13 with mCherry causes aberrant virion morphogenesis.
    J Gen Virol 2017 Sep 20. Epub 2017 Sep 20.
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
    Vaccinia virus produces two distinct infectious virions; the single-enveloped intracellular mature virus (IMV), which remains in the cell until cell lysis, and the double-enveloped extracellular enveloped virus (EEV), which mediates virus spread. The latter is derived from a triple-enveloped intracellular enveloped virus (IEV) precursor, which is transported to the cell periphery by the kinesin-1 motor complex. This transport involves the viral protein A36 as well as F12 and E2. Read More

    Heparan sulfate as a receptor for poxvirus infections and as a target for antiviral agents.
    J Gen Virol 2017 Sep 21. Epub 2017 Sep 21.
    2​Cancer and Vascular Biology Group, ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia.
    To establish the importance of virus-heparan sulfate (HS) interactions in virus infectivity, the poxvirus vaccinia virus (VACV) was used, as it binds HS and has both enveloped virus (EV) and non-enveloped mature virus (MV) forms. Initial studies showed that heparin inhibited plaque formation by both MV-rich WR and EV-rich IHD-J strains of VACV, with the EV-rich strain also losing trademark 'comet'-shaped plaques. However, using GFP-tagged EV and MV forms of VACV, based on IC50 values, heparin was 16-fold more effective at inhibiting the infectivity of the EV form compared to the MV form. Read More

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