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

    Vaccinia virus C9 ankyrin-repeat/F-box protein is a newly identified antagonist of the type I interferon-induced antiviral state.
    J Virol 2018 Feb 14. Epub 2018 Feb 14.
    Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA
    Type I interferons (IFNs) induce expression of more than 300 cellular genes that provide protection against viruses and other pathogens. For survival, viruses evolved defenses to prevent the IFN response or counteract the IFN-induced antiviral state. However, because viruses and cells co-evolved, the dynamic relationship between virus and host is difficult to discern. Read More

    Cross-priming induces immunodomination in the presence of viral MHC class I inhibition.
    PLoS Pathog 2018 Feb 14;14(2):e1006883. Epub 2018 Feb 14.
    Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
    Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8+ T cells (CTLs), which is well-illustrated by our prior studies on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice is dominated by a single peptide antigen presented by H-2Kb. Read More

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

    Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes.
    PLoS One 2018 31;13(1):e0190869. Epub 2018 Jan 31.
    Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, Milan, Italy.
    A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. Read More

    Development of a Safe and Effective Vaccinia Virus Oncolytic Vector WR-Δ4 with a Set of Gene Deletions on Several Viral Pathways.
    Mol Ther Oncolytics 2018 Mar 5;8:27-40. Epub 2017 Dec 5.
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Darwin 3, Madrid, 28049, Spain.
    Despite the effectiveness of classic treatments and available diagnostic tools, cancer continues to be a leading world health problem, with devastating cancer-related death rates. Advances in oncolytic virotherapy have shown promise as potentially effective treatment options in the fight against cancer. The poxviruses have many features that make them an attractive platform for the development of oncolytic vectors, with some candidates currently in clinical trials. Read More

    Extension of the viral ecology in humans using viral profile hidden Markov models.
    PLoS One 2018 19;13(1):e0190938. Epub 2018 Jan 19.
    Dept. of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    When human samples are sequenced, many assembled contigs are "unknown", as conventional alignments find no similarity to known sequences. Hidden Markov models (HMM) exploit the positions of specific nucleotides in protein-encoding codons in various microbes. The algorithm HMMER3 implements HMM using a reference set of sequences encoding viral proteins, "vFam". Read More

    Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments.
    PLoS One 2018 19;13(1):e0188453. Epub 2018 Jan 19.
    Department of Medical Microbiology & Immunology and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
    Edward Jenner and his contemporaries believed that his variolae vaccinae originated in horses and molecular analyses show that modern vaccinia virus (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based vaccine might provide a superior alternative. Since HPXV may be extinct and the only specimen of HPXV that has been identified is unavailable for investigation, we explored whether HPXV could be obtained by large-scale gene synthesis. Read More

    Identification of Poxvirus Genome Uncoating and DNA Replication Factors with Mutually Redundant Roles.
    J Virol 2018 Jan 17. Epub 2018 Jan 17.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA
    Genome uncoating is essential for replication of most viruses. For poxviruses, the process is divided into two stages: removal of the envelope allowing early gene expression, and breaching of the core wall allowing DNA release, replication and late gene expression. Subsequent studies showed that the host proteasome and the viral D5 protein, which has an essential role in DNA replication, are required for vaccinia virus (VACV) genome uncoating. Read More

    Myxoma Virus M083 is a virulence factor which mediates systemic dissemination.
    J Virol 2018 Jan 17. Epub 2018 Jan 17.
    Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
    Poxviruses are large, DNA viruses whose protein capsid is surrounded by one or more lipid envelopes. Embedded into these lipid envelopes are three conserved viral proteins which are thought to mediate binding of virions to target cells. While the function of these proteins has been studied, their specific roles during the pathogenesis of poxviral disease remains largely unclear. Read More

    TheInhibitory Effect of Ectromelia Virus Infection on Innate and Adaptive Immune Properties of GM-CSF-Derived Bone Marrow Cells Is Mouse Strain-Independent.
    Front Microbiol 2017 19;8:2539. Epub 2017 Dec 19.
    Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
    Ectromelia virus (ECTV) belongs to thegenus of thefamily and is a natural pathogen of mice. Certain strains of mice are highly susceptible to ECTV infection and develop mousepox, a lethal disease similar to smallpox of humans caused by variola virus. Currently, the mousepox model is one of the available small animal models for investigating pathogenesis of generalized viral infections. Read More

    Genetic analysis of L1R myristoylated protein of Capripoxviruses reveals structural homogeneity among poxviruses.
    Infect Genet Evol 2018 Mar 4;58:224-231. Epub 2018 Jan 4.
    Division of Virology, ICAR-Indian Veterinary Research Institute, Mukteswar 263 138, Nainital, Uttarakhand, India.
    Sheeppox virus (SPPV) and goatpox virus (GTPV) are members of the genus Capripoxvirus (CaPV) of the family Poxviridae. CaPVs are responsible for important contagious diseases of small ruminants that are enzootic to the Indian sub-continent, Central and Northern Africa and the Middle East. In the present study, the sequence and phylogenetic analysis of the L1R gene of sixteen CaPV isolates (seven SPPV and nine GTPV) from India were performed along with 3D homology modeling of the L1R protein. Read More

    A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling.
    PLoS Pathog 2017 Dec 15;13(12):e1006779. Epub 2017 Dec 15.
    Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana- Champaign, Urbana, IL, United States of America.
    Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤ 30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. Read More

    Recombinant Vaccinia virus-coded interferon inhibitor B18R: Expression, refolding and a use in a mammalian expression system with a RNA-vector.
    PLoS One 2017 7;12(12):e0189308. Epub 2017 Dec 7.
    National Center for Biotechnology, Astana, Kazakhstan.
    B18R protein of Vaccinia virus binds to type I interferons and inhibits activation of interferon-mediated signal transduction. Cells which have unimpaired interferon signaling such as primary cell cultures or some industrially important cell lines are capable of development of an antiviral state. An establishment of the antiviral state limits replication of RNA-viruses and can suppress replication of RNA vectors. Read More

    Comparative analysis of avian poxvirus genomes, including a novel poxvirus from lesser flamingos (Phoenicopterus minor), highlights the lack of conservation of the central region.
    BMC Genomics 2017 Dec 6;18(1):947. Epub 2017 Dec 6.
    Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
    Background: Avian poxviruses are important pathogens of both wild and domestic birds. To date, seven isolates from subclades A and B and one from proposed subclade E, have had their genomes completely sequenced. The genomes of these isolates have been shown to exhibit typical poxvirus genome characteristics with conserved central regions and more variable terminal regions. Read More

    Suppression of Poxvirus Replication by Resveratrol.
    Front Microbiol 2017 17;8:2196. Epub 2017 Nov 17.
    Division of Biology, Kansas State University, Manhattan, KS, United States.
    Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. Read More

    Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample.
    Sci Rep 2017 Nov 28;7(1):16472. Epub 2017 Nov 28.
    Veterinary Diagnostic Laboratory, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
    Poxviruses are large DNA viruses with varying zoonotic potential, and are recognised in a broad range of wildlife. Although poxviruses have been detected in kangaroos, their genetic relationships to poxviruses in other animals and humans is not well understood. Here, we present a novel genome sequence of a marsupial poxvirus, the Eastern grey kangaroopox virus (EKPV-NSW), isolated from a wild eastern grey kangaroo. Read More

    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 thedominate across all species examined, and ssDNA viruses, notably the, 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 2018 Mar 20;30(2):256-259. Epub 2017 Nov 20.
    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 Dec 11;35(52):7222-7230. 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.
    Thefamily 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 thefamily, 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 Confirm that Vaccinia Virus SSB Plays an Essential Role in Viral Replication.
    J Virol 2018 Jan 2;92(2). Epub 2018 Jan 2.
    Departments of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA
    Vaccinia virus is unusual among DNA viruses in replicating exclusively in the cytoplasm of infected cells. The single-stranded DNA (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 (vΔI3) lacking the I3 open reading frame (ORF). 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

    Transcriptome analysis of sheep oral mucosa response to Orf virus infection.
    PLoS One 2017 26;12(10):e0186681. Epub 2017 Oct 26.
    State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Public Health of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
    Contagious ecthyma is a highly contagious disease with worldwide distribution, which is caused by the Orf virus (ORFV) belonging to the Parapoxvirus. To study the alteration of host gene expression in response to ORFV infection at the transcriptional level, several young small-tailed Han sheep were inoculated with ORFV, and their oral mucosa tissue samples (T0, T3, T7 and T15) were collected on day 0, 3, 7 and 15 after ORFV infection respectively. RNA-seq transcriptome comparisons were performed, showing that 1928, 3219 and 2646 differentially expressed genes (DEGs) were identified among T3 vs. Read More

    Emergence of carp edema virus (CEV) and its significance to European common carp and koi Cyprinus carpio.
    Dis Aquat Organ 2017 Oct;126(2):155-166
    Centre for Environment, Fisheries and Aquaculture Science (Cefas), Weymouth, DT4 8UB, UK.
    Carp edema virus disease (CEVD), also known as koi sleepy disease, is caused by a poxvirus associated with outbreaks of clinical disease in koi and common carp Cyprinus carpio. Originally characterised in Japan in the 1970s, international trade in koi has led to the spread of CEV, although the first recognised outbreak of the disease outside of Japan was not reported until 1996 in the USA. In Europe, the disease was first recognised in 2009 and, as detection and diagnosis have improved, more EU member states have reported CEV associated with disease outbreaks. 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

    Maternal and Fetal Outcomes Among Pregnant Women With Human Monkeypox Infection in the Democratic Republic of Congo.
    J Infect Dis 2017 Oct;216(7):824-828
    L'Institut National de Recherche Biomédicale.
    Human monkeypox is an endemic disease in rain-forested regions of central Democratic Republic of Congo. We report fetal outcomes for 1 of 4 pregnant women who participated in an observational study at the General Hospital of Kole (Sankuru Province), where 222 symptomatic subjects were followed between 2007 and 2011. Of the 4 pregnant women, 1 gave birth to a healthy infant, 2 had miscarriages in the first trimester, and 1 had fetal death, with the macerated stillborn showing diffuse cutaneous maculopapillary skin lesions involving the head, trunk and extremities, including palms of hands and soles of feet. 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 ofand, 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 thefamily, namely Cowpox virus. Read More

    HIV-1 gp120 and Modified Vaccinia Virus Ankara (MVA) gp140 Boost Immunogens Increase Immunogenicity of a DNA/MVA HIV-1 Vaccine.
    J Virol 2017 Dec 30;91(24). Epub 2017 Nov 30.
    GeoVax, Inc., Smyrna, Georgia, USA
    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 virus Ankara (MVA) expressing HIV-1 Env on virus-like particles. In this study, 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

    Transcriptional analysis of the putative glycosyltransferase gene (amv248) of the Amsacta moorei entomopoxvirus.
    Virus Res 2018 01 8;243:25-30. Epub 2017 Oct 8.
    Department of Biology, Faculty of Sciences, Karadeniz Technical University, Trabzon, Turkey. Electronic address:
    Amsacta moorei entomopoxvirus (AMEV), the most studied member of the genus Betaentomopoxvirus, was initially isolated from Red Hairy caterpillar larvae, Amsacta moorei. According to genome sequence and previous studies it was shown that amv248 encodes a putative glycosyltransferase that is the only conserved attachment protein in betaentomopoxviruses. Transcriptional analysis of the amv248 gene by RT-PCR and qPCR showed that transcription starts at 6h post infection (hpi). 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

    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

    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

    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 Nov;216(9):1080-1090
    US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
    Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara-Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device.

    Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg of PENNVAX-G DNA delivered intramuscularly by Biojector or electroporation at baseline and week 4 followed by intramuscular injection of 108 plaque forming units of MVA-CMDR at weeks 12 and 24. The open-label part A was conducted in the United States, 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 12 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 11 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

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