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    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 May;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, INSERM
    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 towards 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

    Spread of poxviruses in livestock in Brazil associated with cases of double and triple infection.
    Arch Virol 2017 May 17. Epub 2017 May 17.
    Laboratório Nacional Agropecuário de Minas Gerais, Avenida Rômulo Joviano, Centro, Pedro Leopoldo, Minas Gerais, 33600-000, Brazil.
    The objective of this work is to describe the distribution of outbreaks of vaccinia virus (VACV), pseudocowpox virus (PCPV), and bovine papular stomatitis virus (BSPV) in Brazil. The Official Laboratory of the Brazilian Ministry of Agriculture received 89 samples from different locations in Brazil in 2015 and 2016 for diagnosis of vesicular and exanthematous disease. Poxvirus coinfections occurred in 11 out of 33 outbreaks, including the first reported triple infection by BPSV, PCPV, and VACV. Read More

    Deletion of the Vaccinia B1 Kinase Reveals Essential Functions of this Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2.
    J Virol 2017 May 17. Epub 2017 May 17.
    Nebraska Center for Virology, the School of Veterinary Medicine and Biomedical Sciences, and the School of Biological Sciences, University of Nebraska, Lincoln, NE, USA.
    The vaccinia B1 kinase is highly conserved among poxviruses and is essential for the viral lifecycle. B1 exhibits a remarkable degree of similarity to VRKs, a family of cellular kinases, suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1 and VRKs have been demonstrated to target a shared substrate, the DNA binding protein BAF, elucidating a signaling pathway important for both mitosis and the antiviral response. Read More

    Molluscum Contagiosum Virus MC159 abrogates cIAP1-NEMO interactions and inhibits NEMO polyubiquitination.
    J Virol 2017 May 17. Epub 2017 May 17.
    Department of Microbiology, University of Illinois, Urbana-Champaign, Illinois, USA
    Molluscum contagiosum virus (MCV) is a dermatotropic poxvirus that causes benign skin lesions. MCV lesions persist because of virally-encoded immune evasion molecules that inhibit anti-viral responses. The MCV MC159 protein suppresses NF-κB activation, a powerful anti-viral response, via interactions with the NEMO subunit of the IKK complex. Read More

    Reverse Genetics of Newcastle Disease Virus.
    Methods Mol Biol 2017 ;1602:141-158
    Southeast Poultry Research Laboratory, United States Department of Agriculture, 934 College Station Rd, Athens, GA, 30605, USA.
    Reverse genetics allows for the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique enables genetic manipulation and cloning of viral genomes, gene mutation through site-directed mutagenesis, along with gene insertion or deletion, among other studies. An in vitro infection-based system including the highly attenuated vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid, was successfully developed to rescue genetically modified Newcastle disease viruses in 1999. Read More

    Rescue of Sendai Virus from Cloned cDNA.
    Methods Mol Biol 2017 ;1602:103-110
    Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA.
    Sendai virus (SeV) is a non-segment negative-sense RNA virus that naturally infects and causes pneumonia in mice. As a prototypic member of the family Paramyxoviridae, SeV has been characterized well, and these studies revealed numerous traits of paramyxovirus biology. The reverse genetics system to rescue SeV was first established in 1995. Read More

    Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus.
    Methods Mol Biol 2017 ;1602:83-102
    The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK.
    We have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV genome is inserted into the vaccinia virus genome under the control of a T7 promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has the advantage that modifications can be introduced into the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. Here, we describe the use of transient dominant selection as a method for introducing modifications into the IBV cDNA that has been successfully used for the substitution of specific nucleotides, deletion of genomic regions, and exchange of complete genes. Read More

    Subclinical bovine vaccinia: An important risk factor in the epidemiology of this zoonosis in cattle.
    Res Vet Sci 2017 Apr 6;114:233-235. Epub 2017 Apr 6.
    Laboratório de Pesquisa em Virologia Animal, Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, Brazil. Electronic address:
    Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV) that mainly affects lactating cows and dairy farm milkers. The epidemiological role(s) of other cattle categories such as dry cows, bulls, and heifers in BV remains unclear. This study was performed to investigate VACV in affected dairy cattle herds and perifocal farms during an outbreak in Brazil. Read More

    Enhanced Production of Enveloped Viruses in BST-2-deficient Cell Lines.
    Biotechnol Bioeng 2017 May 12. Epub 2017 May 12.
    College of Life Science and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
    Despite all the advantages that cell-cultured influenza vaccines have over egg-based influenza vaccines, the inferior productivity of cell-culture systems is a major drawback that must be addressed. BST-2 (tetherin) is a host restriction factor which inhibits budding-out of various enveloped viruses from infected host cells. We developed BST-2-deficient MDCK and Vero cell lines to increase influenza virus release in cell culture. Read More

    Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human melanoma in vitro model: studying immunogenic cell death, dendritic cell maturation and interaction with cytotoxic T lymphocytes.
    Onco Targets Ther 2017 2;10:2389-2401. Epub 2017 May 2.
    First Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany.
    Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). Read More

    Development of an animal model of progressive vaccinia in nu/nu mice and the use of bioluminescence imaging for assessment of the efficacy of monoclonal antibodies against vaccinial B5 and L1 proteins.
    Antiviral Res 2017 May 8;144:8-20. Epub 2017 May 8.
    Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.
    Bioluminescence imaging (BLI) was used to follow dissemination of recombinant vaccinia virus (VACV) expressing luciferase (IHD-J-Luc) in BALB/c nu/nu mice treated post-challenge with monoclonal antibodies (MAbs) against L1 and B5 VACV proteins in a model of Progressive Vaccinia (PV). Areas Under the flux Curve (AUC) were calculated for viral loads in multiple organs in individual mice. Following scarification with 10(5) pfu, IHD-J-Luc VACV undergoes fast replication at the injection site and disseminates rapidly to the inguinal lymph nodes followed by spleen, liver, and axillary lymph nodes within 2-3 days and before primary lesions are visible at the site of scarification. Read More

    Cross-sectional study involving healthcare professionals in a Vaccinia virus endemic area.
    Vaccine 2017 Jun 8;35(25):3281-3285. Epub 2017 May 8.
    Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil. Electronic address:
    Orthopoxviruses (OPV) are emerging viruses with great importance in human and veterinary medicine, such as Vaccinia virus (VACV), which causes outbreaks of bovine vaccinia (BV) in South America. The clinical aspects of BV are similar to other vesicular infections, complicating the clinical diagnosis. This cross-sectional study evaluated the knowledge of Healthcare Professionals about BV and revealed their unpreparedness about BV in a VACV hyper-endemic area in Brazil, highlighting the public health issues associated with VACV infections. Read More

    Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins.
    J Virol 2017 May 10. Epub 2017 May 10.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
    The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Read More

    Dok-1 and Dok-2 are required to maintain herpes simplex virus 1-specific CD8(+) T cells in a murine model of ocular infection.
    J Virol 2017 May 10. Epub 2017 May 10.
    INRS-Institut Armand-Frappier, Laval, Québec, CANADA
    Dok-1 and Dok-2 negatively regulate responses downstream of several immune receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins are essential in the formation of memory CD8(+) T cells to an exogenous epitope expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the control of viral infection is unknown. Herein, we investigated the role of Dok proteins in modulating the immune response against herpes simplex virus 1 (HSV-1) in a mouse model of ocular infection. Read More

    Deletion of the K1L gene results in a vaccinia virus that is less pathogenic due to muted innate immune responses, yet still elicits protective immunity.
    J Virol 2017 May 10. Epub 2017 May 10.
    Department of Microbiology,
    All viruses strategically alter the anti-viral immune response to their benefit. The vaccinia virus (VACV) K1 protein has multiple immunomodulatory effects in tissue culture models of infection, including NF-κB antagonism. However, the effect of K1 during animal infection is poorly understood. Read More

    Evolutionary cancer-favoring engineered vaccinia virus for metastatic hepatocellular carcinoma.
    Oncotarget 2017 Apr 20. 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

    Recombinant vaccinia vector-based vaccine (Tiantan) boosting a novel HBV subunit vaccine induced more robust and lasting immunity in rhesus macaques.
    Vaccine 2017 Jun 6;35(25):3347-3353. Epub 2017 May 6.
    Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, People's Republic of China. Electronic address:
    This study explored several prime-boost strategies in rhesus macaques using various novel hepatitis B virus (HBV) vaccines that showed promise as prophylactic and therapeutic approaches in our previous study using in a mouse model. The tested vaccines included an HBV particle subunit (HBSS1) vaccine and the recombinant vaccinia (RVJSS1) or adenoviral (rAdSS1) vector-based vaccines containing S (1-223aa) and PreS1 (21-47aa). The strength and maintenance of humoral activity (IgG and neutralizing antibodies) and cellular immunity (interferon-γ production assessed by IFN-γ enzyme-linked immunosorbent spot (ELISpot) assay) were investigated in a longitudinal study following various vaccination protocols until 79weeks post-vaccination. Read More

    Cowpox virus: What's in a Name?
    Viruses 2017 May 9;9(5). Epub 2017 May 9.
    Bundeswehr Institute of Microbiology, Neuherbergstr 11, 80937 Munich, Germany.
    Traditionally, virus taxonomy relied on phenotypic properties; however, a sequence-based virus taxonomy has become essential since the recent requirement of a species to exhibit monophyly. The species Cowpox virus has failed to meet this requirement, necessitating a reexamination of this species. Here, we report the genomic sequences of nine Cowpox viruses and, by combining them with the available data of 37 additional genomes, confirm polyphyly of Cowpox viruses and find statistical support based on genetic data for more than a dozen species. Read More

    RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.
    Dev Cell 2017 May;41(3):315-329.e7
    Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:
    RhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Read More

    Vaccinia Virus Proteins A36 and F12/E2 Show Strong Preferences for Different KLC Isoforms.
    Traffic 2017 May 9. Epub 2017 May 9.
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
    Vaccinia virus (VACV) utilises microtubule-mediated trafficking at several stages of its life cycle, of which virus egress is the most intensely studied. During egress VACV proteins A36, F12 and E2 are involved in kinesin-1 interactions, however the roles of these proteins remain poorly understood. A36 forms a direct link between virions and kinesin-1, yet in its absence VACV egress still occurs on microtubules. Read More

    Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis.
    Mol Ther Oncolytics 2017 Jun 21;5:41-61. Epub 2017 Mar 21.
    Department of Biochemistry, Biocenter, University of Wuerzburg, 97074 Wuerzburg, Germany.
    Oncolytic vaccinia virus (VACV) therapy is an alternative cancer treatment modality that mediates targeted tumor destruction through a tumor-selective replication and an induction of anti-tumor immunity. We developed a humanized tumor mouse model with subcutaneous human tumors to analyze the interactions of VACV with the developing tumors and human immune system. A successful systemic reconstitution with human immune cells including functional T cells as well as development of tumors infiltrated with human T and natural killer (NK) cells was observed. Read More

    Cellular Immune Response to DNA and Vaccinia Prime-boost Immunization Kills Plasmodium yoelii Infected Hepatocytes In Vitro.
    Pathog Dis 2017 May 5. Epub 2017 May 5.
    Malaria Program, Naval Medical Research Center, Silver Spring, Maryland, USA.
    Background: Plasmid DNA encoding Plasmodium yoelii circumsporozoite protein (PyCSP) and boosted with recombinant vaccinia virus containing the PyCSP elicited significant protective immunity in mice that was primarily mediated by CD8+ T-cell responses directed to P. yoelii -infected hepatocytes. This study was to further explore protection using in vitro cultures of P. Read More

    In vivo targeting of protein antigens to dendritic cells using anti-DEC-205 single chain antibody improves HIV Gag specific CD4(+) T cell responses protecting from airway challenge with recombinant vaccinia-gag virus.
    Immun Inflamm Dis 2017 Mar 13. Epub 2017 Mar 13.
    Laboratory of Vaccinology/Biobanking of The Chantal Biya International Reference Center for Research on The Prevention and Management of HIV/AIDS, Yaounde, Cameroon.
    Introduction: Targeting antigens to dendritic cells (DCs) in vivo via a DC-restricted endocytic receptor, DEC205, has been validated to enhance immunity in several vaccine platforms. Particularly atttractive is selected delivery of proteins to DCs in vivo because it enables proteins to be more immunogenic and provides a cheaper and effective way for repeated immunizations.

    Methods: In this study, we tested the efficacy of a single chain antibody to DEC205 (scDEC) to deliver protein antigens selectively to DCs in vivo and to induce protective immunity. Read More

    IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection.
    J Immunol 2017 Jun 3;198(11):4341-4351. Epub 2017 May 3.
    Pediatric Rheumatology, University of Colorado-Denver, Aurora, CO 80045
    The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1(-/-)) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. Read More

    Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication.
    Cell Rep 2017 May;19(5):1022-1032
    Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK. Electronic address:
    In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Read More

    Oncolytic efficacy of thymidine kinase-deleted vaccinia virus strain Guang9.
    Oncotarget 2017 Apr 15. Epub 2017 Apr 15.
    Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
    Oncolytic virotherapy is being developed as a promising platform for cancer therapy due to its ability to lyse cancer cells in a tumor-specific manner. Vaccinia virus has been used as a live vaccine in the smallpox eradication program and now is being potential in cancer therapy with a great safety profile. Vaccinia strain Guang9 (VG9) is an attenuated Chinese vaccinia virus and its oncolytic efficacy has been evaluated in our previous study. Read More

    A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.
    Virology 2017 Jul 28;507:242-256. Epub 2017 Apr 28.
    Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, USA; School of Life Sciences, Arizona State University, Tempe, AZ, USA. Electronic address:
    Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. Read More

    Vaccination with recombinant Modified Vaccinia Ankara (MVA) viruses expressing single African horse sickness virus VP2 antigens induced cross-reactive virus neutralising antibodies (VNAb) in horses when administered in combination.
    Vaccine 2017 Apr 21. Epub 2017 Apr 21.
    The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, UK. Electronic address:
    African horse sickness is a lethal viral disease of equids transmitted by biting midges of the Genus Culicoides. The disease is endemic to sub-Saharan Africa but outbreaks of high mortality and economic impact have occurred in the past in non-endemic regions of Africa, Asia and Southern Europe. Vaccination is critical for the control of this disease but only live attenuated vaccines are currently available. Read More

    Preclinical Development of BCG.HIVA(, Harboring an Integrative Expression Vector, for a HIV-TB Pediatric vaccine. Enhancement of Stability and Specific HIV-1 T-cell Immunity.
    Hum Vaccin Immunother 2017 Apr 20. Epub 2017 Apr 20.
    a AIDS Research Group, Hospital Clínic/IDIBAPS-HIVACAT. School of Medicine University of Barcelona , Barcelona , Catalonia , Spain.
    One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. Read More

    Distinct roles of vaccinia virus NF-kB inhibitor proteins A52, B15 and K7 in the immune response.
    J Virol 2017 Apr 19. Epub 2017 Apr 19.
    Department of Molecular and Cellular Biology and Biocomputing Unit, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain
    Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their use as vaccine vectors. To test the role of poxvirus NF-κB pathway inhibitors A52, B15 and K7 in immunity, we deleted their genes in a NYVAC vaccinia virus strain that expresses HIV-1 clade C antigens. After infection of mice, ablation of A52R, B15R and K7R increased dendritic cell, natural killer cell and neutrophil migration as well as chemokine/cytokine expression. Read More

    T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response.
    JCI Insight 2017 Apr 20;2(8). Epub 2017 Apr 20.
    Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. Read More

    Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by affecting the subcellular localization of clock proteins in mammalian cells.
    Biochem Biophys Res Commun 2017 May 13;487(2):320-326. Epub 2017 Apr 13.
    Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 16499, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 16499, Republic of Korea. Electronic address:
    In the eukaryotic circadian clock machinery, negative feedback repression of CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME (CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise regulation of the time-dependent nuclear entry of circadian repressors is crucial to generating normal circadian rhythms. Here, we sought to identify novel kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased screening using red fluorescent protein (RFP)-tagged human kinome expression plasmids in mammalian cells. Read More

    Review of poxvirus: emergence of monkeypox.
    Med Sante Trop 2017 Feb;27(1):29-39
    Service de dermatologie, HIA Sainte-Anne, Toulon, France.
    This article reviews the different types of poxvirus infections. Smallpox, although eradicated, must continue to be monitored because of the potential risk of accidental or voluntary (by bioterrorism) reintroduction. Monkeypox and cowpox viruses are considered to be emergent today ; their high risk of dissemination is due to the increase in international transport as well as trends for new animals as pets and the loss of vaccinal protection against smallpox. Read More

    Efficient and Robust Paramyxoviridae Reverse Genetics Systems.
    mSphere 2017 Mar-Apr;2(2). Epub 2017 Mar 29.
    Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i. Read More

    IL-21 is required for CD4 memory formation in response to viral infection.
    JCI Insight 2017 Apr 6;2(7):e90652. Epub 2017 Apr 6.
    Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, and.
    IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. Read More

    Transient dominant host-range selection using Chinese hamster ovary cells to generate marker-free recombinant viral vectors from vaccinia virus.
    Biotechniques 2017 Apr 1;62(4):183-187. Epub 2017 Apr 1.
    Experimental Therapeutics Laboratory, Hanson Institute and Sansom Institute, Adelaide, Australia.
    Recombinant vaccinia viruses (rVACVs) are promising antigen-delivery systems for vaccine development that are also useful as research tools. Two common methods for selection during construction of rVACV clones are (i) co-insertion of drug resistance or reporter protein genes, which requires the use of additional selection drugs or detection methods, and (ii) dominant host-range selection. The latter uses VACV variants rendered replication-incompetent in host cell lines by the deletion of host-range genes. Read More

    Isolation and identification of compounds from Kalanchoe pinnata having human alphaherpesvirus and vaccinia virus antiviral activity.
    Pharm Biol 2017 Dec;55(1):1586-1591
    a Department of Microbiology and Molecular Biology , Brigham Young University , Provo , UT , USA.
    Context: Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage. Read More

    Absence of vaccinia virus detection in a remote region of the Northern Amazon forests, 2005-2015.
    Arch Virol 2017 Apr 7. Epub 2017 Apr 7.
    Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
    Vaccinia virus (VACV) circulates in Brazil and other South America countries and is responsible for a zoonotic disease that usually affects dairy cattle and humans, causing economic losses and impacting animal and human health. Furthermore, it has been detected in wild areas in the Brazilian Amazon. To better understand the natural history of VACV, we investigated its circulation in wildlife from French Guiana, a remote region in the Northern Amazon forest. Read More

    Monocytic myeloid-derived suppressor cells regulate T-cell responses against vaccinia virus.
    Eur J Immunol 2017 Apr 6. Epub 2017 Apr 6.
    Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
    Vaccinia virus (VV) can potently activate NK- and T-cell responses, leading to efficient viral control and generation of long-lasting protective immunity. However, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. We have previously shown that granulocytic myeloid-derived suppressor cells (g-MDSCs) can suppress the NK-cell response to VV infection. Read More

    Generating Recombinant Vesicular Stomatitis Viruses for Use as Vaccine Platforms.
    Methods Mol Biol 2017 ;1581:203-222
    Department of Microbiology and National Emerging Infectious Disease Laboratory, Boston University School of Medicine, Boston, MA, USA.
    The unique properties of vesicular stomatitis virus (VSV) make it a promising vaccine platform. With the advent of plasmid-based approaches to generate recombinant VSV viruses that express glycoproteins of other viruses, researchers now have the means to generate vaccine candidates targeting a variety of human pathogens. This chapter gives a general overview of the workings of VSV as a vaccine platform and provides a detailed protocol for the generation of recombinant VSV from plasmids. Read More

    Poxvirus Safety Analysis in the Pregnant Mouse Model, Vaccinia, and Raccoonpox Viruses.
    Methods Mol Biol 2017 ;1581:121-129
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
    Poxviruses cause many diseases in humans and animals worldwide, and there is a need for vaccines with improved safety and good efficacy. In addition, poxvirus vectors are widely used as recombinant vaccines for various infectious diseases and as recombinant and oncolytic vaccines for cancer. One concern with poxvirus vaccine vectors is that some poxviruses can infect a developing fetus and cause fetal loss or congenital disease. Read More

    Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector.
    Methods Mol Biol 2017 ;1581:97-119
    The Jenner Institute, University of Oxford, Research Bldg., Old Road Campus, ORCRB, Oxford, OX3 7DQ, UK.
    The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to two people per million vaccinated. Modified Vaccinia virus Ankara (MVA) is an attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. MVA can encode one or more foreign antigens and thus can function as a multivalent vaccine. Read More

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