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    Coral-associated viral communities show high levels of diversity and host auxiliary functions.
    PeerJ 2017 17;5:e4054. Epub 2017 Nov 17.
    Australian Institute of Marine Science, Townsville, Queensland, Australia.
    Stony corals (Scleractinia) are marine invertebrates that form the foundation and framework upon which tropical reefs are built. The coral animal associates with a diverse microbiome comprised of dinoflagellate algae and other protists, bacteria, archaea, fungi and viruses. Using a metagenomics approach, we analysed the DNA and RNA viral assemblages of seven coral species from the central Great Barrier Reef (GBR), demonstrating that tailed bacteriophages of the Caudovirales dominate across all species examined, and ssDNA viruses, notably the Microviridae, are also prevalent. Read More

    An unusual presentation of pseudocowpox associated with an outbreak of pustular ulcerative vulvovaginitis in a Swedish dairy herd.
    J Vet Diagn Invest 2017 Nov 1:1040638717737126. Epub 2017 Nov 1.
    Departments of Microbiology (Blomqvist, Ullman, Renström, Leijon), National Veterinary Institute, Uppsala, Sweden.
    Species Pseudocowpox virus (PCPV; family Poxviridae) is known to cause pustular cutaneous disease in cattle. We describe an outbreak of pseudocowpox with an unusual clinical picture in a free-stall dairy herd of ~80 cows. Approximately 90% of the cows had vesicles, erosions, papules, and scabs on the vulva and vaginal mucosa. Read More

    Outbreak investigation and molecular diagnosis of Lumpy skin disease among livestock in Saudi Arabia 2016.
    Transbound Emerg Dis 2017 Nov 17. Epub 2017 Nov 17.
    Department of Animal Resources, Ministry of Environment, Water and Agriculture, Riyadh, Saudi Arabia.
    Lumpy skin disease (LSD) is a highly infectious disease of cattle caused by a virus of the Capripoxvirus genus in the family Poxviridae. The disease is a major concern for the dairy industry in Saudi Arabia. In this study, an outbreak of LSD in cattle herds was detected in Saudi Arabia in 2016. Read More

    Identification of host DEAD-box RNA helicases that regulate cellular tropism of oncolytic Myxoma virus in human cancer cells.
    Sci Rep 2017 Nov 16;7(1):15710. Epub 2017 Nov 16.
    The Biodesign Institute; Center for Immunotherapy, Vaccines, and Virotherapy; Arizona State University, Tempe, AZ, 85287-5401, USA.
    Myxoma virus (MYXV), a Leporipoxvirus, is being developed as an oncolytic virotherapeutic for the treatment of a variety of human cancers. MYXV tropism for human cancer cells is largely mediated by intracellular signaling networks that regulate viral replication or innate antiviral response pathways. Thus, MYXV is fully or partially permissive for the majority of human cancer cells that harbor defects in antiviral signaling, but a minority are nonpermissive because the virus infection aborts before its completion. 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

    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

    Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism.
    Viruses 2017 Nov 10;9(11). Epub 2017 Nov 10.
    Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany.
    DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To elucidate adaptation mechanisms of poxviruses, we isolated cowpox virus particles from a rat and passaged them five times in a human and a rat cell line. Read More

    Seasonal recurrence of cowpox virus outbreaks in captive cheetahs (Acinonyx jubatus).
    PLoS One 2017 9;12(11):e0187089. Epub 2017 Nov 9.
    Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
    Cowpox virus infections in captive cheetahs (Acinonyx jubatus) with high morbidity and mortality have already been reported in the UK and Russia in the 1970s. However, most of the reported cases have been singular events. Here, we report a total of five cowpox virus outbreaks in cheetahs in the same safari park in Denmark between 2010 and 2014. Read More

    Poxvirus Host Range Genes and Virus-Host Spectrum: A Critical Review.
    Viruses 2017 Nov 7;9(11). Epub 2017 Nov 7.
    Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
    The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each member of the Poxviridae family, the spectrum of the host is variable, where certain viruses can infect a large range of hosts, while others are restricted to only one host species. Read More

    Validation of a pan-orthopox real-time PCR assay for the detection and quantification of viral genomes from nonhuman primate blood.
    Virol J 2017 Nov 3;14(1):210. Epub 2017 Nov 3.
    Division of Medicine, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD, 21702-5011, USA.
    Background: In 1980, smallpox disease was eradicated from nature and Variola virus, the etiological agent of smallpox, was confined to two laboratories, one located in Russia (Moscow) later moved to VECTOR (Novosibirsk, Siberia) and one in the United States (CDC Atlanta). Vaccinations among the general public ceased shortly after the successful eradication campaign, resulting in an increasingly immunologically susceptible population. Because of the possibility of intentional reintroduction of Variola virus and the emergence of other pathogenic poxviruses, there is a great need for the development of medical countermeasures to treat poxvirus disease. 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

    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

    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

    Viral diversity and abundance in polluted waters in Kampala, Uganda.
    Water Res 2017 Dec 6;127:41-49. Epub 2017 Oct 6.
    Department of Civil and Environmental Engineering, Michigan State University, East Lansing, MI, 48824, USA. Electronic address:
    Waterborne viruses are a significant cause of human disease, especially in developing countries such as Uganda. A total of 15 virus-selective samples were collected at five sites (Bugolobi Wastewater Treatment Plant (WWTP) influent and effluent, Nakivubo Channel upstream and downstream of the WWTP, and Nakivubo Swamp) in July and August 2016. Quantitative PCR and quantitative RT-PCR was performed to determine the concentrations of four human viruses (adenovirus, enterovirus, rotavirus, and hepatitis A virus) in the samples. Read More

    A Next-Generation Sequencing Approach Uncovers Viral Transcripts Incorporated in Poxvirus Virions.
    Viruses 2017 Oct 13;9(10). Epub 2017 Oct 13.
    Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany.
    Transcripts are known to be incorporated in particles of DNA viruses belonging to the families of Herpesviridae and Mimiviridae, but the presence of transcripts in other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we first established a next-generation-sequencing (NGS)-based protocol, enabling the unbiased identification of transcripts in virus particles. Subsequently, we applied our protocol to analyze RNA in an emerging zoonotic member of the Poxviridae family, namely Cowpox virus. 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

    Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine.
    PLoS Negl Trop Dis 2017 Oct 4;11(10):e0005958. Epub 2017 Oct 4.
    Department of Pathobiological Sciences, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
    Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). 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

    Complete genomic characterisation of two novel poxviruses (WKPV and EKPV) from western and eastern grey kangaroos.
    Virus Res 2017 Oct 27;242:106-121. Epub 2017 Sep 27.
    School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia. Electronic address:
    Poxviruses have previously been detected in macropods with cutaneous papillomatous lesions, however to date, no comprehensive analysis of a poxvirus from kangaroos has been performed. Here we report the genome sequences of a western grey kangaroo poxvirus (WKPV) and an eastern grey kangaroo poxvirus (EKPV), named for the host species from which they were isolated, western grey (Macropus fuliginosus) and eastern grey (Macropus giganteus) kangaroos. Poxvirus DNA from WKPV and EKPV was isolated and entire coding genome regions determined through Roche GS Junior and Illumina Miseq sequencing, respectively. Read More

    Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16-STING-Type I IFN Pathway and AIM2 Sensor.
    J Immunol 2017 Nov 25;199(9):3293-3305. Epub 2017 Sep 25.
    Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
    Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. 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

    Characterization of a PKR inhibitor from the pathogenic ranavirus, Ambystoma tigrinum virus, using a heterologous vaccinia virus system.
    Virology 2017 Nov 14;511:290-299. Epub 2017 Sep 14.
    School of Life Sciences, and The Biodesign Institute, Center for Infectious Diseases and Vaccinology Arizona State University, Tempe, AZ 85287-5001, USA. Electronic address:
    Ambystoma tigrinum virus (ATV) (family Iridoviridae, genus Ranavirus) was isolated from diseased tiger salamanders (Ambystoma tigrinum stebbinsi) from the San Rafael Valley in southern Arizona, USA in 1996. Genomic sequencing of ATV, as well as other members of the genus, identified an open reading frame that has homology to the eukaryotic translation initiation factor, eIF2α (ATV eIF2α homologue, vIF2αH). Therefore, we asked if the ATV vIF2αH could also inhibit PKR. Read More

    Efficacy and immunogenicity of recombinant swinepox virus expressing the truncated S protein of a novel isolate of porcine epidemic diarrhea virus.
    Arch Virol 2017 Dec 15;162(12):3779-3789. Epub 2017 Sep 15.
    College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China.
    Porcine epidemic diarrhea virus (PEDV) causes significant loss to the swine industry. The emergence of novel PEDV strains in recent years has decreased the effectiveness of PEDV vaccines. We have developed a live recombinant vaccine, a swinepox virus vector that expresses a truncated S protein (rSPV-St) from a recent PEDV strain, SQ2014, and evaluated its immunogenicity and effectiveness in a swine model. Read More

    Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells.
    PLoS Pathog 2017 Sep 14;13(9):e1006569. Epub 2017 Sep 14.
    Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America.
    Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM) provide robust protection in a variety of infectious models. Read More

    Vaccinia Virus Encodes a Novel Inhibitor of Apoptosis That Associates with the Apoptosome.
    J Virol 2017 Dec 14;91(23). Epub 2017 Nov 14.
    Department of Microbiology, University of Illinois, Urbana, Illinois, USA
    Apoptosis is an important antiviral host defense mechanism. Here we report the identification of a novel apoptosis inhibitor encoded by the vaccinia virus (VACV) M1L gene. M1L is absent in the attenuated modified vaccinia virus Ankara (MVA) strain of VACV, a strain that stimulates apoptosis in several types of immune cells. Read More

    Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates.
    PLoS One 2017 13;12(9):e0184718. Epub 2017 Sep 13.
    Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
    Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. Read More

    Immunogenicity of ORFV-based vectors expressing the rabies virus glycoprotein in livestock species.
    Virology 2017 Nov 9;511:229-239. Epub 2017 Sep 9.
    Animal Disease Research and Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA; South Dakota Center for Biologics Research and Commercialization (SD-CBRC), South Dakota State University, Brookings, SD 57007, USA. Electronic address:
    The parapoxvirus Orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. Here we describe the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). The RABV-G gene was inserted in the ORFV024 or ORFV121 gene loci, which encode for IMPs that are unique to parapoxviruses and inhibit activation of the NF-κB signaling pathway. Read More

    Nonintegrating Gene Therapy Vectors.
    Hematol Oncol Clin North Am 2017 Oct;31(5):753-770
    AGCTlab.org, Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK. Electronic address:
    Gene delivery vectors that do not rely on host cell genome integration offer several advantages for gene transfer, chiefly the avoidance of insertional mutagenesis and position effect variegation. However, unless engineered for replication and segregation, nonintegrating vectors will dilute progressively in proliferating cells, and are not exempt of epigenetic effects. This article provides an overview of the main nonintegrating viral (adenoviral, adeno-associated viral, integration-deficient retro-lentiviral, poxviral), and nonviral (plasmid vectors, artificial chromosomes) vectors used for preclinical and clinical cell and gene therapy applications. Read More

    Prenylation of viral proteins by enzymes of the host: Virus-driven rationale for therapy with statins and FT/GGT1 inhibitors.
    Bioessays 2017 Oct 8;39(10). Epub 2017 Sep 8.
    School of Systems Biology, George Mason University, Fairfax, VA, USA.
    Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria. Read More

    Active dissemination of cellular antigens by DCs facilitates CD8(+) T-cell priming in lymph nodes.
    Eur J Immunol 2017 Oct;47(10):1802-1818
    Department of Immunology and Veterinary Services, Weizmann Institute of Science, Rehovot, Israel.
    Antigen (Ag) specific activation of naïve T cells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their colocalization in lymph nodes (LNs) appear low. Ag presentation may be delegated from Ag-donor DCs to the abundant resident DCs, but the routes of Ag transfer and how it facilitates T-cell activation remain unclear. We visualized CD8(+) T cell-DC interactions to study the sites, routes, and cells mediating Ag transfer in mice. Read More

    A comparative review of viral entry and attachment during large and giant dsDNA virus infections.
    Arch Virol 2017 Dec 2;162(12):3567-3585. Epub 2017 Sep 2.
    Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden.
    Viruses enter host cells via several mechanisms, including endocytosis, macropinocytosis, and phagocytosis. They can also fuse at the plasma membrane and can spread within the host via cell-to-cell fusion or syncytia. The mechanism used by a given viral strain depends on its external topology and proteome and the type of cell being entered. Read More

    The 5'-poly(A) leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation.
    PLoS Pathog 2017 Aug 30;13(8):e1006602. Epub 2017 Aug 30.
    Division of Biology, Kansas State University, Manhattan, Kansas, United States of America.
    The poly(A) leader at the 5'-untranslated region (5'-UTR) is an unusually striking feature of all poxvirus mRNAs transcribed after viral DNA replication (post-replicative mRNAs). These poly(A) leaders are non-templated and of heterogeneous lengths; and their function during poxvirus infection remains a long-standing question. Here, we discovered that a 5'-poly(A) leader conferred a selective translational advantage to mRNA in poxvirus-infected cells. Read More

    Viruses in cancers among the immunosuppressed.
    Int J Cancer 2017 Dec 13;141(12):2498-2504. Epub 2017 Sep 13.
    Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital, Huddinge, Stockholm, 141 86, Sweden.
    Most cancer forms known to be caused by viruses are increased among the immunosuppressed, but several cancer forms without established viral etiology are also increased, notably nonmelanoma skin carcinoma (NMSC). We followed all 13,429 solid organ transplantation patients in Sweden for cancer occurrence after transplantation. We requested these tumor specimens and sequenced the first 89 specimens received (62 NMSCs, 27 other cancers). Read More

    Efficient and stable production of Modified Vaccinia Ankara virus in two-stage semi-continuous and in continuous stirred tank cultivation systems.
    PLoS One 2017 24;12(8):e0182553. Epub 2017 Aug 24.
    Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
    One important aim in cell culture-based viral vaccine and vector production is the implementation of continuous processes. Such a development has the potential to reduce costs of vaccine manufacturing as volumetric productivity is increased and the manufacturing footprint is reduced. In this work, continuous production of Modified Vaccinia Ankara (MVA) virus was investigated. Read More

    Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus sp.).
    PLoS Negl Trop Dis 2017 Aug 21;11(8):e0005809. Epub 2017 Aug 21.
    US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United States of America.
    Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp. Read More

    [(18)F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection.
    J Virol 2017 Nov 13;91(21). Epub 2017 Oct 13.
    Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
    Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [(18)F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). Read More

    Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice.
    PLoS One 2017 16;12(8):e0183377. Epub 2017 Aug 16.
    Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA, United States of America.
    Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC. Utilizing a recently isolated anti-PC NAb, we produced highly pure soluble PC protein that displayed conformational and linear neutralizing epitopes, interfered with HCMV entry, and was recognized by antibodies induced by HCMV during natural infection. Read More

    Biophysical and Computational Studies of the vCCI:vMIP-II Complex.
    Int J Mol Sci 2017 Aug 16;18(8). Epub 2017 Aug 16.
    Departments of Molecular Cell Biology and Chemistry and Chemical Biology, and the Health Sciences Research Institute, University of California Merced 5200 North Lake Rd, Merced, CA 953402, USA.
    Certain viruses have the ability to subvert the mammalian immune response, including interference in the chemokine system. Poxviruses produce the chemokine binding protein vCCI (viral CC chemokine inhibitor; also called 35K), which tightly binds to CC chemokines. To facilitate the study of vCCI, we first provide a protocol to produce folded vCCI from Escherichia coli (E. Read More

    Droplet digital PCR for rapid enumeration of viral genomes and particles from cells and animals infected with orthopoxviruses.
    Virology 2017 Nov 10;511:19-22. Epub 2017 Aug 10.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address:
    Droplet digital polymerase chain reaction (ddPCR) was adapted for quantifying the number of orthopoxviral genomes in purified virus samples, infected cell lysates and tissues of infected animals. In contrast to the more commonly used qPCR, the newer ddPCR provides absolute numbers of DNA copies in samples without need for standard curves and has the ability to detect rare mutants in a population. The genome/infectious unit ratio for several sucrose gradient-purified orthopoxviruses varied from 5 to 10, which correlated well with values obtained using the Virocyt, a dedicated fluorescence flow cytometer. Read More

    HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers.
    PLoS One 2017 9;12(8):e0181886. Epub 2017 Aug 9.
    The Jenner Institute, University of Oxford, Oxford, United Kingdom.
    Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. Read More

    A parapoxviral virion protein inhibits NF-κB signaling early in infection.
    PLoS Pathog 2017 Aug 7;13(8):e1006561. Epub 2017 Aug 7.
    Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
    Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Read More

    Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis.
    Viruses 2017 Aug 8;9(8). Epub 2017 Aug 8.
    Department of Biological Sciences, Seton Hall University, South Orange, NJ 07039, USA.
    Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Read More

    A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.
    PLoS One 2017 3;12(8):e0181738. Epub 2017 Aug 3.
    Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.
    The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Read More

    Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field.
    J Virol 2017 Oct 27;91(20). Epub 2017 Sep 27.
    CSIRO Health and Biosecurity, Black Mountain Laboratories, Acton, ACT, Australia
    The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Read More

    Transmission dynamics of lumpy skin disease in Ethiopia.
    Epidemiol Infect 2017 Oct 3;145(13):2856-2863. Epub 2017 Aug 3.
    Quantitative Veterinary Epidemiology,Wageningen University & Research,Droevendaalsesteeg 1, 6708 PB Wageningen,The Netherlands.
    Lumpy skin disease (LSD) is a severe disease of cattle caused by a Capripoxvirus and often caused epidemics in Ethiopia and many other countries. This study was undertaken to quantify the transmission between animals and to estimate the infection reproduction ratio in a predominantly mixed crop-livestock system and in intensive commercial herd types. The transmission parameters were based on a susceptible-infectious-recovered (SIR) epidemic model with environmental transmission and estimated using generalized linear models. Read More

    Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells.
    Sci Immunol 2017 May;2(11)
    Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
    Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. Read More

    Two novel poxviruses with unusual genome rearrangements: NY_014 and Murmansk.
    Virus Genes 2017 Dec 31;53(6):883-897. Epub 2017 Jul 31.
    The National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
    The genome sequence and annotation of two novel poxviruses, NY_014 and Murmansk, are presented. Despite being isolated on different continents and from different hosts, the viruses are relatively similar, albeit distinct species. The closest known relative of the novel viruses is Yoka poxvirus. Read More

    Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry.
    J Immunol 2017 Sep 31;199(5):1923-1932. Epub 2017 Jul 31.
    Immunologie des Infections Virales et des Maladies Auto-immunes (ImVA)/Infrastructure Nationale pour la Modélisation des Maladies Infectieuses Humaines et les Thérapies Innovantes (IDMIT)/Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA)/Direction de la Recherche Fondamentale (DRF)/Institut des Maladies Emergentes et des Traitements Innovants (IMETI), Université Paris-Sud, INSERM U1184, 92265 Fontenay-Aux-Roses, France;
    The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Read More

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