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https://www.readbyqxmd.com/read/29029254/retrospective-proteomic-analysis-of-serum-after-akhmeta-virus-infection-new-suspect-case-identification-and-insights-into-poxvirus-humoral-immunity
#1
Michael B Townsend, Nadia F Gallardo-Romero, Ekaterine Khmaladze, Neil M Vora, Giorgi Maghlakelidze, Marika Geleishvili, Darin S Carroll, Ginny L Emerson, Mary G Reynolds, P S Satheshkumar
Serologic cross-reactivity, a hallmark of orthopoxvirus (OPXV) infection, makes species-specific diagnosis of infection difficult. In this study, we used a Variola virus (VARV) proteome microarray to characterize and differentiate antibody responses to non-vaccinia OPXV infections from smallpox vaccination. The profile of two-case patients infected with newly discovered OPXV, Akhmeta virus (AKMV), exhibited antibody responses of greater intensity and broader recognition of viral proteins and includes the B21/22 family glycoproteins not encoded by vaccinia virus (VACV) strains used as vaccines...
October 6, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29028182/hypothesis-rna-and-dna-viral-sequence-integration-into-the-mammalian-host-genome-supports-long-term-b-cell-and-t-cell-adaptive-immunity
#2
Julia L Hurwitz, Bart G Jones, Emmanuelle Charpentier, David L Woodland
Viral sequence integration into the mammalian genome has long been perceived as a health risk. In some cases, integration translates to chronic viral infection, and in other instances, oncogenic gene mutations occur. However, research also shows that animal cells can benefit from integrated viral sequences (e.g., to support host cell development or to silence foreign invaders). Here we propose that, comparable with the clustered regularly interspaced short palindromic repeats that provide bacteria with adaptive immunity against invasive bacteriophages, animal cells may co-opt integrated viral sequences to support immune memory...
October 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29021394/hiv-1-gp120-protein-and-mvagp140-boost-immunogens-increase-immunogenicity-of-a-dna-mva-hiv-1-vaccine
#3
Xiaoying Shen, Rahul Basu, Sheetal Sawant, David Beaumont, Sue Fen Kwa, Celia LaBranche, Kelly E Seaton, Nicole L Yates, David C Montefiori, Guido Ferrari, Linda S Wyatt, Bernard Moss, S Munir Alam, Barton F Haynes, Georgia D Tomaras, Harriet L Robinson
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia Ankara (MVA) expressing HIV-1 Env on virus like particles. Here we evaluated whether the addition of a gp120 protein in alum or MVA expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime - MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26 and 40...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020102/dusp3-deletion-in-mice-promotes-experimental-lung-tumour-metastasis-in-a-macrophage-dependent-manner
#4
Maud Vandereyken, Sophie Jacques, Eva Van Overmeire, Mathieu Amand, Natacha Rocks, Céline Delierneux, Pratibha Singh, Maneesh Singh, Camille Ghuysen, Caroline Wathieu, Tinatin Zurashvili, Nor Eddine Sounni, Michel Moutschen, Christine Gilles, Cécile Oury, Didier Cataldo, Jo A Van Ginderachter, Souad Rahmouni
Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel outgrowth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice developed larger lung metastases than littermate controls...
2017: PloS One
https://www.readbyqxmd.com/read/29020058/hiv-transmitted-founder-vaccines-elicit-autologous-tier-2-neutralizing-antibodies-for-the-cd4-binding-site
#5
Nathanael P McCurley, Arban Domi, Rahul Basu, Kevin O Saunders, Celia C LaBranche, David C Montefiori, Barton F Haynes, Harriet L Robinson
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)...
2017: PloS One
https://www.readbyqxmd.com/read/28989096/exploiting-2a-peptides-to-elicit-potent-neutralizing-antibodies-by-a-multi-subunit-herpesvirus-glycoprotein-complex
#6
Felix Wussow, Flavia Chiuppesi, Zhuo Meng, Joy Martinez, Jenny Nguyen, Peter A Barry, Don J Diamond
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...
October 6, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28989031/the-development-of-a-monolith-based-purification-process-for-orthopoxvirus-vaccinia-virus-lister-strain
#7
David Vincent, Petra Kramberger, Rosana Hudej, Aleš Štrancar, Yaohe Wang, Yuhong Zhou, Ajoy Velayudhan
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. In this work, monolith-based capture and polishing chromatographic steps for vaccinia virus Lister strain has been developed...
September 5, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28987424/strategies-to-obtain-multiple-recombinant-modified-vaccinia-ankara-vectors-applications-to-influenza-vaccines
#8
Andrea Barbieri, Maddalena Panigada, Elisa Soprana, Giuseppina Di Mario, Francesco Gubinelli, Valentina Bernasconi, Marta Recagni, Isabella Donatelli, Maria R Castrucci, Antonio G Siccardi
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...
October 4, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28986831/a-cell-cell-fusion-assay-to-assess-arenavirus-envelope-glycoprotein-membrane-fusion-activity
#9
Joanne York, Jack H Nunberg
For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28972080/identifying-host-factors-associated-with-dna-replicated-during-virus-infection
#10
Emigdio D Reyes, Katarzyna Kulej, Neha J Pancholi, Lisa N Akhtar, Daphne C Avgousti, Eui Tae Kim, Daniel K Bricker, Lynn A Spruce, Sarah A Koniski, Steven H Seeholzer, Stuart N Isaacs, Benjamin A Garcia, Matthew D Weitzman
Viral DNA genomes replicating in cells encounter a myriad of host factors that facilitate or hinder viral replication. Viral proteins expressed early during infection modulate host factors interacting with viral genomes, recruiting proteins to promote viral replication, and limiting access to antiviral repressors. Although some host factors manipulated by viruses have been identified, we have limited knowledge of pathways exploited during infection and how these differ between viruses. To identify cellular processes manipulated during viral replication, we defined proteomes associated with viral genomes during infection with adenovirus, herpes simplex virus and vaccinia virus...
October 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28969431/intradermal-hiv-1-dna-immunization-using-needle-free-zetajet-sup-tm-sup-injection-followed-by-hiv-modified-vaccinia-virus-ankara-vaccination-is-safe-and-immunogenic-in-mozambican-young-adults-a-phase-i-randomized-controlled-trial
#11
Edna Omar Viegas, Nelson Tembe, Charlotta Nilsson, Bindiya Meggi, Cremildo Maueia, Orvalho Augusto, Richard Stout, Gabriella Scarlatti, Guido Ferrari, Patricia Earl, Britta Wahren, Sören Andersson, Merlin Robb, Nafissa Osman, Gunnel Biberfeld, Ilesh Jani, Eric Sandström
We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups...
October 2, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28968759/safety-and-immunogenicity-of-pennvax%C3%A2-g-dna-prime-administered-by-biojector%C3%A2-2000-or-cellectra%C3%A2-electroporation-device-with-modified-vaccinia-ankara-cmdr-boost
#12
Julie A Ake, Alexandra Schuetz, Poonam Pegu, Lindsay Wieczorek, Michael A Eller, Hannah Kibuuka, Fredrick Sawe, Leonard Maboko, Victoria Polonis, Nicos Karasavva, David Weiner, Arthur Sekiziyivu, Josphat Kosgei, Marco Missanga, Arne Kroidl, Philipp Mann, Silvia Ratto-Kim, Leigh Anne Eller, Patricia Earl, Bernard Moss, Julie Dorsey-Spitz, Mark Milazzo, G Laissa Ouedraogo, Farrukh Rizvi, Jian Yan, Amir S Khan, Sheila Peel, Niranjan Y Sardesai, Nelson L Michael, Viseth Ngauy, Mary Marovich, Merlin L Robb
Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX®-G DNA/ MVA-CMDR prime-boost HIV vaccine, with intramuscular DNA delivery by either Biojector® 2000 needle free injection system (Biojector) or by CELLECTRA® electroporation device. Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg PENNVAX®-G DNA delivered IM by Biojector or electroporation at baseline and week 4 followed by IM injection of 108 pfu MVA-CMDR at week 12 and 24...
September 2, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28963881/selective-recruitment-of-nucleoporins-on-vaccinia-virus-factories-and-the-role-of-nup358-in-viral-infection
#13
Deepak Khuperkar, Ashish Kamble, Aditi Singh, Arya Ghate, Renuka Nawadkar, Arvind Sahu, Jomon Joseph
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. Here, we report that the nucleoporins Nup62 and Nup358 localize to the cytoplasmic viral factories (VFs). Nup358 was targeted to the VFs at 6h post-infection (hpi), whereas Nup62, along with the previously reported translation factors such as eIF4E, eIF3η and G3BP1, was recruited to the VFs at 8 hpi...
September 27, 2017: Virology
https://www.readbyqxmd.com/read/28960132/in-vivo-monitoring-of-infectious-diseases-in-living-animals-using-bioluminescence-imaging
#14
Asheesh Gupta, Pinar Avci, Mahdi Karimi, Magesh Sadasivam, Wanessa C Antunes-Melo, Elisa Carrasco, Michael R Hamblin
Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative...
September 29, 2017: Virulence
https://www.readbyqxmd.com/read/28951871/recombinant-vaccinia-viruses-coding-transgenes-of-apoptosis-inducing-proteins-enhance-apoptosis-but-not-immunogenicity-of-infected-tumor-cells
#15
Olga Koval, Galina Kochneva, Anastasiya Tkachenko, Olga Troitskaya, Galina Sivolobova, Antonina Grazhdantseva, Anna Nushtaeva, Elena Kuligina, Vladimir Richter
Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28948956/construction-establishment-of-two-minigenome-rescue-systems-for-chandipura-virus-driven-by-recombinant-vaccinia-virus-expressing-t7-polymerase
#16
Prasenjit Chakraborty
BACKGROUND & OBJECTIVES: Chandipura virus (CHPV) is an emerging pathogenic rhabdovirus with a high case fatality rate. There are no reports of a minigenome system for CHPV, which could help its study without having to use the infectious agent. This study was, therefore, undertaken for the establishment of T7 polymerase-driven minigenome system for CHPV. METHODS: The minigenome rescue system for CHPV consists of three helper plasmids expressing the nucleocapsid protein (N), phosphoprotein (P) and large protein (L) based on a recombinant vaccinia virus expressing bacteriophage T7 polymerase (vTF7-3)...
May 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28941620/safety-and-immunogenicity-of-heterologous-prime-boost-immunization-with-viral-vectored-malaria-vaccines-adjuvanted-with-matrix-m%C3%A2
#17
Navin Venkatraman, Nicholas Anagnostou, Carly Bliss, Georgina Bowyer, Danny Wright, Karin Lövgren-Bengtsson, Rachel Roberts, Ian Poulton, Alison Lawrie, Katie Ewer, Adrian V S Hill
The use of viral vectors in heterologous prime-boost regimens to induce potent T cell responses in addition to humoral immunity is a promising vaccination strategy in the fight against malaria. We conducted an open-label, first-in-human, controlled Phase I study evaluating the safety and immunogenicity of Matrix-M adjuvanted vaccination with a chimpanzee adenovirus serotype 63 (ChAd63) prime followed by a modified vaccinia Ankara (MVA) boost eight weeks later, both encoding the malaria ME-TRAP antigenic sequence (a multiple epitope string fused to thrombospondin-related adhesion protein)...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#18
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28938920/oral-vaccination-of-wildlife-using-a-vaccinia-rabies-glycoprotein-recombinant-virus-vaccine-raboral-v-rg-%C3%A2-a-global-review
#19
REVIEW
Joanne Maki, Anne-Laure Guiot, Michel Aubert, Bernard Brochier, Florence Cliquet, Cathleen A Hanlon, Roni King, Ernest H Oertli, Charles E Rupprecht, Caroline Schumacher, Dennis Slate, Boris Yakobson, Anne Wohlers, Emily W Lankau
RABORAL V-RG(®) is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions...
September 22, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28933687/tagging-of-the-vaccinia-virus-protein-f13-with-mcherry-causes-aberrant-virion-morphogenesis
#20
David C J Carpentier, Michael S Hollinshead, Helen A Ewles, Stacey-Ann Lee, Geoffrey L Smith
Vaccinia virus produces two distinct infectious virions; the single-enveloped intracellular mature virus (IMV), which remains in the cell until cell lysis, and the double-enveloped extracellular enveloped virus (EEV), which mediates virus spread. The latter is derived from a triple-enveloped intracellular enveloped virus (IEV) precursor, which is transported to the cell periphery by the kinesin-1 motor complex. This transport involves the viral protein A36 as well as F12 and E2. A36 is an integral membrane protein associated with the outer virus envelope and is the only known direct link between virion and kinesin-1 complex...
September 20, 2017: Journal of General Virology
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