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Virus-specific T cell

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https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#1
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#2
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28210631/immunogenicity-and-cross-protection-in-mice-afforded-by-pandemic-h1n1-live-attenuated-influenza-vaccine-containing-wild-type-nucleoprotein
#3
Andrey Rekstin, Irina Isakova-Sivak, Galina Petukhova, Daniil Korenkov, Igor Losev, Tatiana Smolonogina, Tatiana Tretiak, Svetlana Donina, Svetlana Shcherbik, Tatiana Bousse, Larisa Rudenko
Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28207491/intrastructural-help-improving-the-hiv-1-envelope-antibody-response-induced-by-virus-like-particle-vaccines
#4
Vladimir Temchura, Klaus Überla
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response...
February 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28202771/delayed-differentiation-of-potent-effector-cd8-t-cells-reducing-viremia-and-reservoir-seeding-in-acute-hiv-infection
#5
Hiroshi Takata, Supranee Buranapraditkun, Cari Kessing, James L K Fletcher, Roshell Muir, Virginie Tardif, Pearline Cartwright, Claire Vandergeeten, Wendy Bakeman, Carmen N Nichols, Suteeraporn Pinyakorn, Pokrath Hansasuta, Eugene Kroon, Thep Chalermchai, Robert O'Connell, Jerome Kim, Nittaya Phanuphak, Merlin L Robb, Nelson L Michael, Nicolas Chomont, Elias K Haddad, Jintanat Ananworanich, Lydie Trautmann
CD8(+) T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8(+) T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8(+) T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8(+) T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI)...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28202754/jak-stat-signaling-pathways-and-inhibitors-affect-reversion-of-envelope-mutated-hiv-1
#6
Yudong Quan, Hongtao Xu, Yingshan Han, Thibault Mesplède, Mark A Wainberg
HIV can spread by both cell-free and cell-to-cell transmission. Here, we show that numerous of the amino acid changes in Env that are close to the CD4 binding pocket can affect HIV replication. We generated a number of mutant viruses that were unable to infect T cells as cell-free viruses but were nevertheless able to infect certain T cell lines as cell-associated viruses, followed by reversion to wild type. However, the activation of JAK-STAT signaling pathways caused inhibition of such cell-to-cell infection as well as the reversion of multiple HIV Env mutants that displayed differences in ability to bind to the CD4 receptor...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#7
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202614/virus-specific-cd8-t-cells-infiltrate-melanoma-lesions-and-retain-function-independently-of-pd-1-expression
#8
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/28202026/an-indirect-enzyme-linked-immunosorbent-assay-for-the-identification-of-antibodies-to-senecavirus-a-in-swine
#9
Cheryl M T Dvorak, Zeynep Akkutay-Yoldar, Suzanne R Stone, Steven J P Tousignant, Fabio A Vannucci, Michael P Murtaugh
BACKGROUND: Senecavirus A (SVA), a member of the family Picornaviridae, genus Senecavirus, is a recently identified single-stranded RNA virus closely related to members of the Cardiovirus genus. SVA was originally identified as a cell culture contaminant and was not associated with disease until 2007 when it was first observed in pigs with Idiopathic Vesicular Disease (IVD). Vesicular disease is sporadically observed in swine, is not debilitating, but is significant due to its resemblance to foreign animal diseases, such as foot-and-mouth disease (FMD), whose presence would be economically devastating to the United States...
February 15, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28197337/defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#10
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28194013/potent-single-domain-antibodies-that-arrest-respiratory-syncytial-virus-fusion-protein-in-its-prefusion-state
#11
Iebe Rossey, Morgan S A Gilman, Stephanie C Kabeche, Koen Sedeyn, Daniel Wrapp, Masaru Kanekiyo, Man Chen, Vicente Mas, Jan Spitaels, José A Melero, Barney S Graham, Bert Schepens, Jason S McLellan, Xavier Saelens
Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28191007/antigen-exposure-history-defines-cd8-t-cell-dynamics-and-protection-during-localized-pulmonary-infections
#12
Natalija Van Braeckel-Budimir, Matthew D Martin, Stacey M Hartwig, Kevin L Legge, Vladimir P Badovinac, John T Harty
Unlike systemic infections, little is known about the role of repeated localized infections on (re)shaping pathogen-specific memory CD8 T cell responses. Here, we used primary (1°) and secondary (2°) intranasal influenza virus infections of mice as a model to study intrinsic memory CD8 T cell properties. We show that secondary antigen exposure, relative to a single infection, generates memory CD8 T cell responses of superior magnitude in multiple tissue compartments including blood, spleen, draining lymph nodes, and lung...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28187750/study-on-age-dependent-pre-existing-2009-pandemic-influenza-virus-t-and-b-cell-responses-from-chinese-population
#13
Jin Lv, Zhen-Yong Ren, Ying-Ying Zhang, Yun-E Liu, Jun Gao, Kun Yao, Dan Feng, Zhen-Yuan Li, Xin Feng, Yun-Xi Liu, Na Jia
BACKGROUND: The outbreak of the 2009 H1N1 influenza pandemic (H1N1pdm) affected thousands of people in Mexico and the United States, and spread rapidly throughout the world from April 2009 to July 2010. To explore the age-specific prevalence of seroprotection against H1N1pdm infection, we estimated pre-existing humoral and cellular immunities of residents in Northern China against H1N1pdm and seasonal H1N1 virus in an age-dependent manner. METHODS: Anonymous serum samples were collected from 1425 to 1434 adult healthy individuals before and after the pandemic outbreak, and then grouped by birth year 1913-1990...
February 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28184007/cyclin-f-fbxo1-interacts-with-hiv-1-vif-and-restricts-progeny-virion-infectivity-by-ubiquitination-and-proteasomal-degradation-of-vif-through-scf-cyclin-f-e3-ligase-machinery
#14
Tracy Augustine, Priyanka Chaudhary, Kailash Gupta, Sehbanul Islam, Payel Ghosh, Manas Kumar Santra, Debashis Mitra
Cyclin F, also known as FBXO1, is the largest among all cyclins which oscillates in the cell cycle like other cyclins. Apart from being a G2/M cyclin, Cyclin F functions as the substrate binding subunit of SCFCyclin F E3 ubiquitin ligase. In a gene expression analysis performed to identify novel gene modulations associated with cell cycle dysregulation during HIV-1 infection in CD4+ T cells, we observed down-regulation of Cyclin F (CCNF) gene. Later, using gene over expression and knockdown studies, we identified that Cyclin F negatively influences HIV-1 viral infectivity without any significant impact on virus production...
February 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183713/vaccination-targeting-native-receptors-to-enhance-the-function-and-proliferation-of-chimeric-antigen-receptor-car-modified-t-cells
#15
Miyuki Tanaka, Haruko Tashiro, Bilal Omer, Natasha Lapteva, Jun Ando, Minhtran Ngo, Birju Mehta, Gianpietro Dotti, Paul R Kinchington, Ann M Leen, Claudia Rossig, Cliona M Rooney
PURPOSE: The multiple mechanisms used by solid tumors to suppress tumor-specific immune responses are a major barrier to the success of adoptively-transferred tumor-specific T-cells. Since viruses induce potent innate and adaptive immune responses, we hypothesized that the immunogenicity of viruses could be harnessed for the treatment of solid tumors if virus-specific T-cells (VSTs) were modified with tumor-specific chimeric antigen receptors (CARs). We tested this hypothesis using VZV-specific T-cells (VZVSTs) expressing a CAR for GD2, a disialoganglioside expressed on neuroblastoma and certain other tumors, since the live-attenuated VZV vaccine could be used for in vivo stimulation...
February 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28182361/evaluation-of-line-immunoassay-to-detect-htlv-1-infection-in-an-endemic-area-southwestern-japan-comparison-with-polymerase-chain-reaction-and-western-blot
#16
Kazumi Umeki, Kunihiko Umekita, Yuuki Hashikura, Ikuo Yamamoto, Kazuyoshi Kubo, Yasuhiro Nagatomo, Akihiko Okayama
BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) has been recognized as a cause of adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis, and HTLV-1-associated uveitis. HTLV-1 infection is normally detected by screening for HTLV-1 antibodies, and positive samples are confirmed by Western blot (WB). However, WB fails to confirm some samples that were positive for HTLV-1 antibodies on screening. Line immunoassay (LIA) is commonly used in Europe and Brazil, but not in Japan...
February 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28181505/parp-1-parp-2-double-deficiency-in-mouse-t-cells-results-in-faulty-immune-responses-and-t-lymphomas
#17
Judith Navarro, Beatriz Gozalbo-López, Andrea C Méndez, Françoise Dantzer, Valérie Schreiber, Carlos Martínez, David M Arana, Jordi Farrés, Beatriz Revilla-Nuin, María F Bueno, Coral Ampurdanés, Miguel A Galindo-Campos, Philip A Knobel, Sandra Segura-Bayona, Juan Martin-Caballero, Travis H Stracker, Pedro Aparicio, Margarita Del Val, José Yélamos
The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4(+) and CD8(+) T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death...
February 9, 2017: Scientific Reports
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
#18
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/28179535/a-bivalent-heterologous-dna-virus-like-particles-prime-boost-vaccine-elicits-broad-protection-against-both-groups-1-and-2-influenza-a-viruses
#19
Wenbo Jiang, Shuangshuang Wang, Honglin Chen, Huanhuan Ren, Xun Huang, Guiqin Wang, Ze Chen, Ling Chen, Zhiwei Chen, Paul Zhou
Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus there is a critical need for developing so-called "universal" vaccines that protect against all influenza viruses. In the present study we developed a bivalent heterologous DNA-virus-like particles (VLP) prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge of group 1 (H1, H5 and H9) and group 2 (H3 and H7) viruses with 94% aggregate survival...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179532/a-murine-herpesvirus-closely-related-to-ubiquitous-human-herpesviruses-causes-t-cell-depletion
#20
Swapneel J Patel, Guoyan Zhao, Vinay R Penna, Eugene Park, Elvin J Lauron, Ian B Harvey, Wandy L Beatty, Beatrice Plougastel-Douglas, Jennifer Poursine-Laurent, Daved H Fremont, David Wang, Wayne M Yokoyama
Mouse models of human herpesvirus infections The human roseoloviruses HHV6A, HHV6B, and HHV7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with Roseoloviruses as direct drivers of pathology because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified...
February 8, 2017: Journal of Virology
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