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https://www.readbyqxmd.com/read/29679095/implication-of-the-vrk1-chromatin-kinase-in-the-signaling-responses-to-dna-damage-a-therapeutic-target
#1
REVIEW
Ignacio Campillo-Marcos, Pedro A Lazo
DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR)...
April 20, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29678552/the-immunogenicity-of-recombinant-vaccines-based-on-modified-vaccinia-ankara-mva-viruses-expressing-african-horse-sickness-virus-vp2-antigens-depends-on-the-levels-of-expressed-vp2-protein-delivered-to-the-host
#2
Eva Calvo-Pinilla, Simon Gubbins, Peter Mertens, Javier Ortego, Javier Castillo-Olivares
African horse sickness (AHS) is a lethal equine disease transmitted by Culicoides biting midges and caused by African horse sickness virus (AHSV). AHS is endemic to sub-Saharan Africa, but devastating outbreaks have been recorded periodically outside this region. The perceived risk of an AHS outbreak occurring in Europe has increased following the frequent epidemics caused in ruminants by bluetongue virus, closely related to AHSV. Attenuated vaccines for AHS are considered unsuitable for use in non-endemic countries due bio-safety concerns...
April 17, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29676720/mutagenic-repair-of-double-stranded-dna-breaks-in-vaccinia-virus-genomes-requires-cellular-dna-ligase-iv-activity-in-the-cytosol
#3
Rutger David Luteijn, Ingo Drexler, Geoffrey L Smith, Robert Jan Lebbink, Emmanuel J H J Wiertz
Poxviruses comprise a group of large dsDNA viruses that include members relevant to human and animal health, such as variola virus, monkeypox virus, cowpox virus and vaccinia virus (VACV). Poxviruses are remarkable for their unique replication cycle, which is restricted to the cytoplasm of infected cells. The independence from the host nucleus requires poxviruses to encode most of the enzymes involved in DNA replication, transcription and processing. Here, we use the CRISPR/Cas9 genome engineering system to induce DNA damage to VACV (strain Western Reserve) genomes...
April 20, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29669284/manifold-roles-of-ccr7-and-its-ligands-in-the-induction-and-maintenance-of-bronchus-associated-lymphoid-tissue
#4
Henrike Fleige, Berislav Bosnjak, Marc Permanyer, Jasmin Ristenpart, Anja Bubke, Stefanie Willenzon, Gerd Sutter, Sanjiv A Luther, Reinhold Förster
The processes underlying the development and maintenance of tertiary lymphoid organs are incompletely understood. Using a Ccr7 knockout/knockin approach, we show that spontaneous bronchus-associated lymphoid tissue (BALT) formation can be caused by CCR7-mediated migration defects of dendritic cells (DCs) in the lung. Plt/plt mice that lack the CCR7 ligands CCL19 and CCL21-serine do not form BALT spontaneously because lung-expressed CCL21-leucine presumably suffices to maintain steady-state DC egress. However, plt/plt mice are highly susceptible to modified vaccinia virus infection, showing enhanced recruitment of immune cells as well as alterations in CCR7-ligand-mediated lymphocyte egress from the lungs, leading to dramatically enhanced BALT...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669026/first-in-human-randomized-controlled-trial-of-mosaic-hiv-1-immunogens-delivered-via-a-modified-vaccinia-ankara-vector
#5
Lindsey R Baden, Stephen R Walsh, Michael S Seaman, Yehuda Z Cohen, Jennifer A Johnson, J Humberto Licona, Rachel D Filter, Jane A Kleinjan, Jon A Gothing, Julia Jennings, Lauren Peter, Joseph Nkolola, Peter Abbink, Erica N Borducchi, Marinela Kirilova, Kathryn E Stephenson, Poonam Pegu, Michael A Eller, Hung V Trinh, Mangala Rao, Julie A Ake, Michal Sarnecki, Steven Nijs, Katleen Callewaert, Hanneke Schuitemaker, Jenny Hendriks, Maria G Pau, Frank Tomaka, Bette T Korber, Galit Alter, Raphael Dolin, Patricia L Earl, Bernard Moss, Nelson L Michael, Merlin L Robb, Dan H Barouch
Background: Mosaic immunogens are bioinformatically engineered HIV-1 sequences designed to elicit clade independent coverage against globally circulating HIV-1 strains. Methods: This Phase 1 double-blind, randomized, placebo-controlled trial enrolled healthy HIV uninfected adults who received two doses of a modified vaccinia Ankara (MVA) vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naïve (N=15) and those who had received an HIV-1 vaccine four to six years earlier (Ad26...
April 13, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29655893/comparative-sequence-and-structural-analysis-of-indian-orf-viruses-based-on-major-envelope-immune-dominant-protein-f1l-an-homologue-of-pox-viral-p35-h3-protein
#6
Revanaiah Yogisharadhya, Veerakyathappa Bhanuprakash, Amit Kumar, Mianak Mondal, Sathish Bhadravati Shivachandra
Orf virus (ORFV), a member of the genus Parapoxvirus in the family Poxviridae, is the cause of orf, a highly contagious zoonotic viral disease that affects mainly sheep and goats. In the present study, the sequence and phylogenetic analysis of Indian ORFV isolates (n = 15) from natural outbreaks in sheep and goats belonging to different geographical regions were analysed on the basis of F1L gene along with homology modelling of F1L protein. Multiple sequence alignments revealed highly conserved C-terminus and heterogeneity of N-terminus region of F1L among all orf viruses studied...
April 12, 2018: Gene
https://www.readbyqxmd.com/read/29652929/immunogenicity-and-safety-of-three-consecutive-production-lots-of-the-non-replicating-smallpox-vaccine-mva-a-randomised-double-blind-placebo-controlled-phase-iii-trial
#7
Edgar Turner Overton, Steven J Lawrence, Eva Wagner, Katrin Nopora, Siegfried Rösch, Philip Young, Darja Schmidt, Christian Kreusel, Sonja De Carli, Thomas P Meyer, Heinz Weidenthaler, Nathaly Samy, Paul Chaplin
BACKGROUND: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts. METHODS: The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme...
2018: PloS One
https://www.readbyqxmd.com/read/29625403/inhibition-of-vaccinia-virus-replication-by-nitazoxanide
#8
Sarah E Hickson, Daciana Margineantu, David M Hockenbery, Julian A Simon, Adam P Geballe
Nitazoxanide (NTZ) is an FDA-approved anti-protozoal drug that inhibits several bacteria and viruses as well. However, its effect on poxviruses is unknown. Therefore, we investigated the impact of NTZ on vaccinia virus (VACV). We found that NTZ inhibits VACV production with an EC50 of ~2 μM, a potency comparable to that reported for several other viruses. The inhibitory block occurs early during the viral life cycle, prior to viral DNA replication. The mechanism of viral inhibition is likely not due to activation of intracellular innate immune pathways, such as protein kinase R (PKR) or interferon signaling, contrary to what has been suggested to mediate the effects of NTZ against some other viruses...
April 3, 2018: Virology
https://www.readbyqxmd.com/read/29610341/multiple-nuclear-replicating-viruses-require-the-stress-induced-protein-zc3h11a-for-efficient-growth
#9
Shady Younis, Wael Kamel, Tina Falkeborn, Hao Wang, Di Yu, Robert Daniels, Magnus Essand, Jorma Hinkula, Göran Akusjärvi, Leif Andersson
The zinc finger CCCH-type containing 11A ( ZC3H11A ) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29599502/immunogenicity-and-protection-against-influenza-h7n3-in-mice-by-modified-vaccinia-virus-ankara-vectors-expressing-influenza-virus-hemagglutinin-or-neuraminidase
#10
Clement A Meseda, Vajini Atukorale, Jackeline Soto, Maryna C Eichelberger, Jin Gao, Wei Wang, Carol D Weiss, Jerry P Weir
Influenza subtypes such as H7 have pandemic potential since they are able to infect humans with severe consequences, as evidenced by the ongoing H7N9 infections in China that began in 2013. The diversity of H7 viruses calls for a broadly cross-protective vaccine for protection. We describe the construction of recombinant modified vaccinia virus Ankara (MVA) vectors expressing the hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both Eurasian and North American H7 lineages - A/mallard/Netherlands/12/2000 (H7N3), A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9)...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29599088/a-single-vaccination-with-non-replicating-mva-at-birth-induces-both-immediate-and-long-term-protective-immune-responses
#11
Cédric Cheminay, Jana Körner, Constanze Bernig, Michael Brückel, Markus Feigl, Martin Schletz, Mark Suter, Paul Chaplin, Ariane Volkmann
Newborns are considered difficult to protect against infections shortly after birth, due to their ineffective immune system that shows quantitative and qualitative differences compared to adults. However, here we show that a single vaccination of mice at birth with a replication-deficient live vaccine Modified Vaccinia Ankara [MVA] efficiently induces antigen-specific B- and T-cells that fully protect against a lethal Ectromelia virus challenge. Protection was induced within 2 weeks and using genetically modified mice we show that this protection was mainly T-cell dependent...
March 27, 2018: Vaccine
https://www.readbyqxmd.com/read/29594879/matrix-m%C3%A2-adjuvant-enhances-immunogenicity-of-both-protein-and-modified-vaccinia-virus-ankara-based-influenza-vaccines-in-mice
#12
Sofia E Magnusson, Arwen F Altenburg, Karin Lövgren Bengtsson, Fons Bosman, Rory D de Vries, Guus F Rimmelzwaan, Linda Stertman
Influenza viruses continuously circulate in the human population and escape recognition by virus neutralizing antibodies induced by prior infection or vaccination through accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a vaccine that provides broad protection against different influenza A viruses are under investigation, including use of recombinant (r) viral vectors and adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a promising vaccine vector that efficiently induces B and T cell responses specific for the antigen of interest...
March 28, 2018: Immunologic Research
https://www.readbyqxmd.com/read/29581897/baseline-mapping-of-lassa-fever-virology-epidemiology-and-vaccine-research-and-development
#13
REVIEW
Hoai J Hallam, Steven Hallam, Sergio E Rodriguez, Alan D T Barrett, David W C Beasley, Arlene Chua, Thomas G Ksiazek, Gregg N Milligan, Vaseeharan Sathiyamoorthy, Lisa M Reece
Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family Arenaviridae . It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Seropositive individuals in endemic regions have been shown to have LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and glycoprotein precursor (GPC), suggesting that these will be important vaccine immunogens...
2018: NPJ vaccines
https://www.readbyqxmd.com/read/29581442/a-vaccinia-based-single-vector-construct-multi-pathogen-vaccine-protects-against-both-zika-and-chikungunya-viruses
#14
Natalie A Prow, Liang Liu, Eri Nakayama, Tamara H Cooper, Kexin Yan, Preethi Eldi, Jessamine E Hazlewood, Bing Tang, Thuy T Le, Yin Xiang Setoh, Alexander A Khromykh, Jody Hobson-Peters, Kerrilyn R Diener, Paul M Howley, John D Hayball, Andreas Suhrbier
Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus mosquitoes. The "Sementis Copenhagen Vector" (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe a single-vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci. A single vaccination of mice induces neutralizing antibodies to both viruses in wild-type and IFNAR-/- mice and protects against (i) chikungunya virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and fetal/placental infection in female IFNAR-/- mice, and (iii) Zika virus viremia and testes infection and pathology in male IFNAR-/- mice...
March 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29572470/transcriptomic-signatures-of-nk-cells-suggest-impaired-responsiveness-in-hiv-1-infection-and-increased-activity-post-vaccination
#15
Margaret C Costanzo, Dohoon Kim, Matthew Creegan, Kerri G Lal, Julie A Ake, Jeffrey R Currier, Hendrik Streeck, Merlin L Robb, Nelson L Michael, Diane L Bolton, Nicholas J Steers, Michael A Eller
Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells...
March 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29572367/myocarditis-secondary-to-smallpox-vaccination
#16
Kyle Keinath, Tyler Church, Benjamin Kurth, Edward Hulten
The development of vaccines ushered in the most profound advancement in 20th century medicine, and have widely been regarded as the one of the most important scientific discovery in the history of mankind. However, vaccines are not without risk; reactions can range from injection site reactions to life-threatening anaphylaxis. Among the more serious vaccine-related sequela is myocarditis. Although myocarditis has been reported following many different vaccines, the smallpox vaccine has the strongest association...
March 22, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29568288/serological-evidence-of-orthopoxvirus-circulation-among-equids-southeast-brazil
#17
Iara A Borges, Mary G Reynolds, Andrea M McCollum, Poliana O Figueiredo, Lara L D Ambrosio, Flavia N Vieira, Galileu B Costa, Ana C D Matos, Valeria M de Andrade Almeida, Paulo C P Ferreira, Zélia I P Lobato, Jenner K P Dos Reis, Erna G Kroon, Giliane S Trindade
Since 1999 Vaccinia virus (VACV) outbreaks involving bovines and humans have been reported in Brazil; this zoonosis is known as Bovine Vaccinia (BV) and is mainly an occupational disease of milkers. It was only in 2008 (and then again in 2011 and 2014) however, that VACV was found causing natural infections in Brazilian equids. These reports involved only equids, no infected humans or bovines were identified, and the sources of infections remain unknown up to date. The peculiarities of Equine Vaccinia outbreaks (e...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29561772/the-host-factor-early-growth-response-gene-egr-1-regulates-vaccinia-virus-infectivity-during-infection-of-starved-mouse-cells
#18
Leonardo C de Oliveira, Bruno S A F Brasil, Bethany Unger, Giliane S Trindade, Jonatas S Abrahão, Erna G Kroon, Paula Traktman, Cláudio A Bonjardim
Evolution has equipped poxvirus genomes with the coding capacity for several virus-host interaction products which interfere with host cell gene expression and protein function, creating an adequate intracellular environment for a productive infection. We show here that Vaccinia virus (VACV) induces the expression of the cellular transcription factor EGR-1 (early growth response-1) in Mouse Embryonic Fibroblasts (MEFs) through the MEK (mitogen-activated protein kinase (MAPK)/ERK)/ERK (extracellular signal-regulated kinases) pathway, from 3 to 12 h post infection (h...
March 21, 2018: Viruses
https://www.readbyqxmd.com/read/29558682/characterization-of-murine-antibody-responses-to-vaccinia-virus-envelope-protein-a14-reveals-an-immunodominant-antigen-lacking-of-effective-neutralization-targets
#19
Xiangzhi Meng, Thomas Kaever, Bo Yan, Paula Traktman, Dirk M Zajonc, Bjoern Peters, Shane Crotty, Yan Xiang
Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy...
March 17, 2018: Virology
https://www.readbyqxmd.com/read/29554163/smallpox-vaccine-complications-the-dermatologist-s-role-in-diagnosis-and-management
#20
Janelle Robertson, Jason Susong, Emily B Wong
In 2002, the United States implemented a new program for smallpox vaccinations among military personnel using a live vaccinia virus product. Approximately 2.4 million US military service members and health care workers have since been inoculated, with considerable numbers experiencing adverse reactions. Military dermatologists are at the forefront of describing and treating these reactions, from relatively benign generalized vaccinia (GV) and erythema multiforme (EM) to more severe progressive vaccinia (PV) and eczema vaccinatum (EV)...
February 2018: Cutis; Cutaneous Medicine for the Practitioner
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