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https://www.readbyqxmd.com/read/28219080/survival-of-tissue-resident-memory-t-cells-requires-exogenous-lipid-uptake-and-metabolism
#1
Youdong Pan, Tian Tian, Chang Ook Park, Serena Y Lofftus, Shenglin Mei, Xing Liu, Chi Luo, John T O'Malley, Ahmed Gehad, Jessica E Teague, Sherrie J Divito, Robert Fuhlbrigge, Pere Puigserver, James G Krueger, Gökhan S Hotamisligil, Rachael A Clark, Thomas S Kupper
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8(+) TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes...
February 20, 2017: Nature
https://www.readbyqxmd.com/read/28218453/divergent-roles-of-%C3%AE-and-%C3%AE-actin-isoforms-during-spread-of-vaccinia-virus
#2
N Bishara Marzook, Sharissa L Latham, Helena Lynn, Christopher Mckenzie, Christine Chaponnier, Georges E Grau, Timothy P Newsome
Actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N-terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. Here we show that virus-tipped actin comets are composed of β- and γ-actin. We employed isoform-specific siRNA knockdown to examine the role of the two isoforms in VACV-induced actin comets...
February 20, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28211116/ac-dielectrophoretic-manipulation-and-electroporation-of-vaccinia-virus-using-carbon-nanoelectrode-arrays
#3
Foram Ranjeet Madiyar, Sherry Basset, Omer Farooq, Stefan Rothenburg, Christopher Culbertson, Jun Li
This paper reports the capture and detection of vaccinia virus particles based on AC dielectrophoresis (DEP) and electrochemical impedance measurements employing an embedded vertically aligned carbon nanofiber (VACNF) nanoelectrode array (NEA) versus a macroscopic indium-tin-oxide (ITO) transparent electrode in a "points-and-lid" configuration. The nano-DEP device was fabricated by bonding two SU-8 covered electrodes patterned using photolithography. The bottom electrode contains a 200 × 200 μm(2) active region on a randomly distributed NEA and the top electrode contains a microfluidic channel in SU-8 spin-coated on ITO to guide the flow of the virus solution...
February 17, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28203643/establishing-elements-of-a-synthetic-biology-platform-for-vaccinia-virus-production-biobrick%C3%A2-design-serum-free-virus-production-and-microcarrier-based-cultivation-of-cv-1-cells
#4
Shuchang Liu, Ludmila Ruban, Yaohe Wang, Yuhong Zhou, Darren N Nesbeth
Vaccinia virus (VACV) is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. Industrial production of VACV stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. The CV-1 cell line can be used for VACV propagation and has been used extensively with the CRISPR/Cas9 system for making precise edits of the VACV genome. Here we take first steps toward establishing a scalable synthetic biology platform for VACV production with CV-1 cells featuring standardised biological tools and serum free cell cultivation...
February 2017: Heliyon
https://www.readbyqxmd.com/read/28202614/virus-specific-cd8-t-cells-infiltrate-melanoma-lesions-and-retain-function-independently-of-pd-1-expression
#5
Dan A Erkes, Corinne J Smith, Nicole A Wilski, Sofia Caldeira-Dantas, Toktam Mohgbeli, Christopher M Snyder
It is well known that CD8(+) tumor-infiltrating lymphocytes (TILs) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. Although it is generally assumed that CD8(+) TILs will be tumor-associated Ag (TAA) specific, it is unknown whether CD8(+) T cells with specificity for common pathogens also infiltrate tumors. If so, the presence of these T cells could alter the interpretation of prognostic and diagnostic TIL assays. We compared TAA-specific and virus-specific CD8(+) T cells in the same tumors using murine CMV, a herpesvirus that causes a persistent/latent infection, and vaccinia virus, a poxvirus that is cleared by the host...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28183815/proteomic-screen-for-cellular-targets-of-the-vaccinia-virus-f10-protein-kinase-reveals-that-phosphorylation-of-mdia-regulates-stress-fiber-formation
#6
Matthew D Greseth, Dominique M Carter, Scott S Terhune, Paula Traktman
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. While this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179536/hiv-aids-vaccine-candidates-based-on-replication-competent-recombinant-poxvirus-nyvac-c-kc-expressing-trimeric-gp140-and-gag-derived-vlps-or-lacking-the-viral-molecule-b19-that-inhibits-type-i-interferon-activate-relevant-hiv-1-specific-b-and-t-cell-immune
#7
Juan García-Arriaza, Beatriz Perdiguero, Jonathan L Heeney, Michael S Seaman, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Guido Ferrari, Kathryn E Foulds, Mario Roederer, Steven G Self, Bhavesh Borate, Raphael Gottardo, Sanjay Phogat, Jim Tartaglia, Susan W Barnett, Brian Burke, Anthony D Cristillo, Deborah E Weiss, Carter Lee, Karen V Kibler, Bertram L Jacobs, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban
The non-replicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120), Gag-Pol-Nef antigens (NYVAC-C) showed in phase I clinical trials limited immunogenicity. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in non-human primates immunized with two replicating NYVAC vectors that have been modified by the insertion of K1L and C7L vaccinia viral host-range genes and express clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28159613/the-vaccinia-virus-dna-polymerase-and-its-processivity-factor
#8
REVIEW
Maciej W Czarnecki, Paula Traktman
Vaccinia virus is the prototypic poxvirus. The 192 kilobase double-stranded DNA viral genome encodes most if not all of the viral replication machinery. The vaccinia virus DNA polymerase is encoded by the E9L gene. Sequence analysis indicates that E9 is a member of the B family of replicative polymerases. The enzyme has both polymerase and 3'-5' exonuclease activities, both of which are essential to support viral replication. Genetic analysis of E9 has identified residues and motifs whose alteration can confer temperature-sensitivity, drug resistance (phosphonoacetic acid, aphidicolin, cytosine arabinsode, cidofovir) or altered fidelity...
February 1, 2017: Virus Research
https://www.readbyqxmd.com/read/28157174/myxoma%C3%A2-virus%C3%A2-dsrna%C3%A2-binding%C3%A2-protein%C3%A2-m029%C3%A2-inhibits%C3%A2-the%C3%A2-type%C3%A2-i%C3%A2-ifn-induced%C3%A2-antiviral%C3%A2-state%C3%A2-in%C3%A2-a%C3%A2-highly%C3%A2-species-specific%C3%A2-fashion
#9
Masmudur M Rahman, Grant McFadden
Myxoma virus (MYXV) is Leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader  cellular host range in cultured cells. MYXV is able to efficiently  block all aspects of the type I interferon (IFN)-induced  antiviral  state  in rabbit cells, partially in  human  cells  and  very  poorly  in  mouse  cells.  The mechanism(s) of this species-specific inhibition of  type I IFN-induced antiviral state is not well understood...
February 2, 2017: Viruses
https://www.readbyqxmd.com/read/28155878/immune-signature-of-enhanced-functional-avidity-cd8-t-cells-in-vivo-induced-by-vaccinia-vectored-vaccine
#10
Zhidong Hu, Lingyan Zhu, Jing Wang, Yanmin Wan, Songhua Yuan, Jian Chen, Xiangqing Ding, Chenli Qiu, Xiaoyan Zhang, Chao Qiu, Jianqing Xu
Functional avidity of T cells is a critical determinant for clearing viral infection and eliminating tumor. Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced in vivo are still lacking. Previously, we and others found vaccinia vectored vaccine (VACV) induced antigen-specific CD8(+) T cells with relatively high functional avidity to those from DNA vaccine. Herein, we used functional, immune phenotyping and transcriptomic studies to define the immune signature of these CD8(+) T cells with high functional avidity...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154190/investigating-viruses-during-the-transformation-of-molecular-biology
#11
Bernard Moss
This Reflections article describes my early work on viral enzymes and the discovery of mRNA capping, how my training in medicine and biochemistry merged as I evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970's and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (VACV), a large DNA virus with about 200 genes. The reader may view this article as a work in progress, since I remain actively engaged in research at the NIH notwithstanding 50 memorable years there...
January 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28153101/viral-vector-malaria-vaccines-induce-high-level-t-cell-and-antibody-responses-in-west-african-children-and-infants
#12
Carly M Bliss, Abdoulie Drammeh, Georgina Bowyer, Guillaume S Sanou, Ya Jankey Jagne, Oumarou Ouedraogo, Nick J Edwards, Casimir Tarama, Nicolas Ouedraogo, Mireille Ouedraogo, Jainaba Njie-Jobe, Amidou Diarra, Muhammed O Afolabi, Alfred B Tiono, Jean Baptiste Yaro, Uche J Adetifa, Susanne H Hodgson, Nicholas A Anagnostou, Rachel Roberts, Christopher J A Duncan, Riccardo Cortese, Nicola K Viebig, Odile Leroy, Alison M Lawrie, Katie L Flanagan, Beate Kampmann, Egeruan B Imoukhuede, Sodiomon B Sirima, Kalifa Bojang, Adrian V S Hill, Issa Nébié, Katie J Ewer
Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8(+) T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28153096/hiv-1-conserved-mosaics-delivered-by-regimens-with-integration-deficient-dc-targeting-lentiviral-vector-induce-robust-t-cells
#13
Edmund G Wee, Beatrice Ondondo, Peter Berglund, Jacob Archer, Andrew J McMichael, David Baltimore, Jan H Ter Meulen, Tomáš Hanke
To be effective against HIV type 1 (HIV-1), vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies; nevertheless, induction of robust long-term memory remains challenging...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28137864/entirely-plasmid-based-reverse-genetics-system-for-rotaviruses
#14
Yuta Kanai, Satoshi Komoto, Takahiro Kawagishi, Ryotaro Nouda, Naoko Nagasawa, Misa Onishi, Yoshiharu Matsuura, Koki Taniguchi, Takeshi Kobayashi
Rotaviruses (RVs) are highly important pathogens that cause severe diarrhea among infants and young children worldwide. The understanding of the molecular mechanisms underlying RV replication and pathogenesis has been hampered by the lack of an entirely plasmid-based reverse genetics system. In this study, we describe the recovery of recombinant RVs entirely from cloned cDNAs. The strategy requires coexpression of a small transmembrane protein that accelerates cell-to-cell fusion and vaccinia virus capping enzyme...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28117806/online-size-exclusion-and-ion-exchange-chromatography-on-a-saxs-beamline
#15
Martha E Brennich, Adam R Round, Stephanie Hutin
Biological small angle X-ray scattering (BioSAXS) is a powerful technique in molecular and structural biology used to determine solution structure, particle size and shape, and surface-to-volume ratio of macromolecules. The technique is applicable to a very wide variety of solution conditions spanning a broad range of concentrations, pH values, ionic strengths, temperatures, additives, etc., but the sample is required to be monodisperse. This caveat led to the implementation of liquid chromatography systems on SAXS beamlines...
January 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28098542/detection-of-vaccinia-virus-in-urban-domestic-cats-brazil
#16
Galileu Barbosa Costa, Júlia Bahia Miranda, Gregório Guilherme Almeida, Jaqueline Silva de Oliveira, Mariana Siqueira Pinheiro, Stefanne Aparecida Gonçalves, Jenner Karlisson Pimenta Dos Reis, Ricardo Gonçalves, Paulo César Peregrino Ferreira, Cláudio Antônio Bonjardim, Jônatas Santos Abrahão, Erna Geessien Kroon, Giliane de Souza Trindade
We investigated possible vaccinia virus (VACV) in urban house cats in Brazil. Serum samples from 6 cats were positive for VACV by PCR, indicating likely VACV circulation among house cats in urban areas of Brazil. This finding highlights the importance of epidemiologic surveillance to avoid outbreaks among urban human populations.
February 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28081250/cutaneous-deficiency-of-filaggrin-and-stat3-exacerbates-vaccinia-disease-in-vivo
#17
Yong He, Ishrat Sultana, Kazuyo Takeda, Jennifer L Reed
RATIONALE: Defects in filaggrin and STAT3 are associated with atopic dermatitis (AD) and susceptibility to severe skin infection. METHODS: We evaluated skin infection with the current smallpox vaccine, ACAM-2000, in immunosuppressed mice with combined cutaneous deficiency in filaggrin and STAT3. In parallel, early events post-infection with ACAM-2000 were investigated in cultured keratinocytes in which filaggrin expression was knocked down via siRNA. RESULTS: Immunosuppressed, filaggrin-deficient mice, treated with the topical STAT3 inhibitor Stattic® prior to ACAM-2000 infection, demonstrated rapid weight loss, prolonged vaccinia burden in skin, and dermatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28079473/protective-immunity-against-influenza-in-hla-a2-transgenic-mice-by-modified-vaccinia-virus-ankara-vectored-vaccines-containing-internal-influenza-proteins
#18
Giuseppina Di Mario, Ester Sciaraffia, Marzia Facchini, Francesco Gubinelli, Elisa Soprana, Maddalena Panigada, Valentina Bernasconi, Bruno Garulli, Antonio Siccardi, Isabella Donatelli, Maria R Castrucci
BACKGROUND: The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses...
January 12, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28067508/coherent-brightfield-microscopy-provides-the-spatiotemporal-resolution-to-study-early-stage-viral-infection-in-live-cells
#19
Yi-Fan Huang, Guan-Yu Zhuo, Chun-Yu Chou, Cheng-Hao Lin, Wen Chang, Chia-Lung Hsieh
Viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. Due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. Here, we use coherent brightfield (COBRI) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. By detecting intrinsic scattered light via imaging-based interferometry, COBRI microscopy allows us to track the motion of a single vaccinia virus particle with nanometer spatial precision (<3 nm) in 3D and microsecond temporal resolution (up to 100,000 frames per second)...
January 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28063045/induction-and-analysis-of-bronchus-associated-lymphoid-tissue
#20
Henrike Fleige, Reinhold Förster
Bronchus-associated lymphoid tissue (BALT) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of T cells in the lung. To explore the mechanisms and instructive signals controlling BALT neogenesis we used both, a single dose of vaccinia virus MVA and repeated inhalations of heat-inactivated Pseudomonas aeruginosa (P. aeruginosa). Intranasal administration of both pathogens induces highly organized BALT but distinct pathways and molecules are used to promote the development of BALT...
2017: Methods in Molecular Biology
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