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https://www.readbyqxmd.com/read/29652930/tissue-maintenance-of-cmv-specific-inflationary-memory-t-cells-by-il-15
#1
Nicolas S Baumann, Nicole Torti, Suzanne P M Welten, Isabel Barnstorf, Mariana Borsa, Katharina Pallmer, Jennifer D Oduro, Luka Cicin-Sain, Koichi Ikuta, Burkhard Ludewig, Annette Oxenius
Cytomegalovirus (CMV) infection induces an atypical CD8 T cell response, termed inflationary, that is characterised by accumulation and maintenance of high numbers of effector memory like cells in circulation and peripheral tissues-a feature being successfully harnessed for vaccine purposes. Although stability of this population depends on recurrent antigen encounter, the requirements for prolonged survival in peripheral tissues remain unknown. Here, we reveal that murine CMV-specific inflationary CD8 T cells are maintained in an antigen-independent manner and have a half-life of 12 weeks in the lung tissue...
April 13, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29650438/hepatitis-e-virus-infection-mimicking-acute-graft-rejection-in-a-liver-transplant-recipient
#2
M Allaire, C Bazille, J Selves, E Salamé, M Altieri
INTRODUCTION: In liver transplant (LT) patients, hepatitis E virus (HEV) can lead to acute liver failure, chronic hepatitis and graft cirrhosis. Few data on graft rejection associated with HEV are available and are subject to discussion. CASE REPORT: Here we report the case of a 58-year-old male patient who underwent LT in July 2015 for cirrhosis due to NASH and chronic alcohol intake complicated by hepatocellular carcinoma. LT was performed with a deceased donor isogroup and a mismatch CMV (donor+ and recipient-)...
April 10, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29624457/low-seroprevalence-of-neutralizing-antibodies-targeting-two-clade-f-aav-in-humans
#3
Jeff L Ellsworth, Michael O'Callaghan, Hillard Rubin, Albert Seymour
To assess the therapeutic utility of AAVHSC15 and AAVHSC17, two recently described Clade F adeno-associated viruses (AAVs), the seroprevalence of neutralizing antibodies (NAbs) to these AAVs was assessed in a representative human population and compared to that of AAV9. NAb levels were measured in 100 unique human sera of different races (34, Black, 33 Caucasian, and 33 Hispanic) and sex (49% female, 51% male) collected within the United States. Fifty-six sera were tested in Huh7 cells and 44 sera were tested in 2V6...
March 2018: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29588542/human-cytomegalovirus-reprogrammes-haematopoietic-progenitor-cells-into-immunosuppressive-monocytes-to-achieve-latency
#4
Dihan Zhu, Chaoyun Pan, Jingxue Sheng, Hongwei Liang, Zhen Bian, Yuan Liu, Phong Trang, Jianguo Wu, Fenyong Liu, Chen-Yu Zhang, Ke Zen
The precise cell type hosting latent human cytomegalovirus (HCMV) remains elusive. Here, we report that HCMV reprogrammes human haematopoietic progenitor cells (HPCs) into a unique monocyte subset to achieve latency. Unlike conventional monocytes, this monocyte subset possesses higher levels of B7-H4, IL-10 and inducible nitric oxide synthase (iNOS), a longer lifespan and strong immunosuppressive capacity. Cell sorting of peripheral blood from latently infected human donors confirms that only this monocyte subset, representing less than 0...
April 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29574509/linkage-disequilibrium-and-functional-analysis-of-pre1-insertion-together-with-snps-in-the-promoter-region-of-igfbp7-gene-in-different-pig-breeds
#5
Qingyan Wu, Hao Yu, Wenzhen Wei, Yunyun Cheng, Shan Huang, Hongyu Shi, Songcai Liu, Jichao Xia, Hongyao Jia, Linlin Hao
Polymorphisms in regions upstream of transcription initiation site may modify the transcriptional activity of target genes by changing promoter activity. This study aims to determine whether or not polymorphisms at porcine IGFBP7 promoter region affect gene expression. In this study, eight SNPs and one PRE1 insertion in this region were first confirmed. The PRE1 insertion was widespread in 20 Chinese indigenous breeds, but was not observed in three commercial breeds. A perfect linkage disequilibrium, consisting of six of those SNPs and a PRE1, was observed with two haplotypes (h1 and h2) in five pig breeds...
March 25, 2018: Journal of Applied Genetics
https://www.readbyqxmd.com/read/29563123/murine-cmv-induces-type-1-ifn-that-impairs-differentiation-of-mdscs-critical-for-transplantation-tolerance
#6
Anil Dangi, Lei Zhang, Xiaomin Zhang, Xunrong Luo
Clinical tolerance without immunosuppression has now been achieved for organ transplantation, and its scope will likely continue to expand. In this context, a previously understudied and now increasingly relevant area is how microbial infections might affect the efficacy of tolerance. A highly prevalent and clinically relevant posttransplant pathogen is cytomegalovirus (CMV). Its impact on transplantation tolerance and graft outcomes is not well defined. Employing a mouse model of CMV (MCMV) infection and allogeneic pancreatic islet transplantation in which donor-specific tolerance was induced by infusing donor splenocytes rendered apoptotic by treatment with ethylenecarbodiimide, we investigated the effect of CMV infection on transplantation tolerance induction...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29563122/epigenetic-programming-of-t-cells-impacts-immune-reconstitution-in-hematopoietic-stem-cell-transplant-recipients
#7
Kristine Hardy, Corey Smith, Wen Juan Tu, Robert McCuaig, Archana Panikkar, Vijayendra Dasari, Fan Wu, Siok-Keen Tey, Geoffrey R Hill, Rajiv Khanna, Sudha Rao
Immune reconstitution following hematopoietic stem cell transplantation (HSCT) is critical in preventing harmful sequelae in recipients with cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying immune reconstitution kinetics, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8+ T cells from HCST recipients with different immune reconstitution efficiencies. CMV-specific T cells from HSCT recipients with stable antiviral immunity expressed higher levels of interferon/defense response and cell cycle genes in an interconnected network involving PI3KCG , STAT5B , NFAT , RBPJ , and lower HDAC6 , increasing chromatin accessibility at the enhancer regions of immune and T-cell receptor signaling pathway genes...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29547547/navigating-the-host-cell-response-during-entry-into-sites-of-latent-cytomegalovirus-infection
#8
REVIEW
Matthew J Murray, Nicholas E Peters, Matthew B Reeves
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection-where the virus establishes an infection in an absence of many gene products specific for lytic infection-these initial interactions are crucial events...
March 16, 2018: Pathogens
https://www.readbyqxmd.com/read/29546767/characterization-of-phenyl-pyrimidine-derivatives-that-inhibit-cytomegalovirus-immediate-early-gene-expression
#9
Koh-Hei Yamada, Ryuichi Majima, Toyofumi Yamaguchi, Naoki Inoue
Background Previously, we established a reporter cell line for human cytomegalovirus and screened anti-human cytomegalovirus compounds using the cell line. In this study, we characterized one of the identified compounds, 2,4-diamino-6-(4-methoxyphenyl)pyrimidine (coded as 35C10). Methods 50% Effective concentrations (EC50s) and 50% cytotoxic concentrations (CC50s) of 35C10 and its derivatives in human fibroblasts were determined by X-gal staining of the cells infected with human cytomegalovirus Towne strain expressing β-galactosidase...
January 2018: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/29545802/potential-beneficial-effects-of-cytomegalovirus-infection-after-transplantation
#10
REVIEW
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29532473/derivation-of-the-clonal-cell-lines-from-siberian-sturgeon-acipenser-baerii-head-kidney-cell-lines-and-its-applicability-to-foreign-gene-expression-and-virus-culture
#11
J H Ryu, M S Kim, J H Kang, D H Kim, Y K Nam, S P Gong
This study was conducted to establish and characterize the clonal-cell lines from Siberian sturgeon Acipenser baerii head-kidney tissues and to evaluate its applicability as a research tool. From the culture of A. baerii head-kidney derived cells, 10 cell lines were established first and then eight clonal-cell lines were derived from clonal growth and colony expansion of two cell lines that showed significant high colony-forming ability. All eight clonal-cell lines were morphologically similar and grew stably under monolayer culture but their growth rates were significantly different...
March 12, 2018: Journal of Fish Biology
https://www.readbyqxmd.com/read/29524699/the-effects-of-smad3-on-acth-secreting-pituitary-adenoma-development-cell-proliferation-apoptosis-and-hormone-secretion
#12
Yong-Zhi Zhou, Chu-Zhong Li, Hua Gao, Ya-Zhuo Zhang
OBJECTIVE: Down-regulation of Smad3 results in the formation of tumors both in vivo and in vitro. However, little is known about the effect of Smad3 on adrenocorticotropic hormone -secreting pituitary adenomas (ACTH-PAs). Our objective was to study the expression and effect of Smad3 in ACTH-PAs and its possible mechanisms. METHODS: Smad3, pSmad3, and Smad2 proteins were detected in samples from 5 normal anterior pituitaries and 18 ACTH-PAs by Western blot and immunohistochemical analysis...
March 7, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29506153/il-7-unveils-pathogen-specific-t-cells-by-enhancing-antigen-recall-responses
#13
Nadia Terrazzini, Paola Mantegani, Florian Kern, Claudio Fortis, Anna Mondino, Stefano Caserta
Background: IL-7 promotes the generation, expansion and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown. Methods: Here we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens...
February 28, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29491009/il-15-promotes-polyfunctional-nk-cell-responses-to-influenza-by-boosting-il-12-production
#14
Helen R Wagstaffe, Carolyn M Nielsen, Eleanor M Riley, Martin R Goodier
IL-15 is a key regulator of NK cell maintenance and proliferation and synergizes with other myeloid cell-derived cytokines to enhance NK cell effector function. At low concentrations, trans -presentation of IL-15 by dendritic cells can activate NK cells, whereas at higher concentrations it can act directly on NK cells, independently of accessory cells. In this study, we investigate the potential for IL-15 to boost responses to influenza virus by promoting accessory cell function. We find that coculture of human PBMCs with inactivated whole influenza virus (A/Victoria/361/2011) in the presence of very low concentrations of IL-15 results in increased production of myeloid cell-derived cytokines, including IL-12, IFN-α2, GM-CSF, and IL-1β, and an increased frequency of polyfunctional NK cells (defined by the expression of two or more of CD107a, IFN-γ, and CD25)...
February 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29486604/low-seroprevalence-of-neutralizing-antibodies-targeting-two-clade-f-aav-in-humans
#15
Jeff L Ellsworth, Michael OCallaghan, Hillard Rubin, Albert Seymour
To assess the therapeutic utility of AAVHSC15 and AAVHSC17, two recently described Clade F adeno-associated viruses, the seroprevalence of neutralizing antibodies to these AAVs was assessed in a representative human population and compared to that of AAV9. Neutralizing antibody levels were measured in 100 unique human sera of different races (34:33:33, Black:Caucasian:Hispanic) and sex (49% Female, 51% Male) collected within the United States. Fifty-six sera were tested in HuH7 cells and 44 sera were tested in 2V6...
February 27, 2018: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29470680/changes-in-skeletal-muscle-and-body-weight-on-sleeping-beauty-transposon-mediated-transgenic-mice-overexpressing-pig-migf-1
#16
Bo Gao, Wei Wang, Han Wu, Cai Chen, Dan Shen, Saisai Wang, Wei Chen, Li Zhang, Shuheng Chan, Chengyi Song
Insulin-like growth factor (IGF-I) is an important growth factor in mammals, but the functions of the local muscle-specific isoform of insulin-like growth factor 1 (mIGF-1) to skeletal muscle development have rarely been reported. To determine the effect of pig mIGF-1 on body development and muscle deposition in vivo and to investigate the molecular mechanisms, the transgenic mouse model was generated which can also provide experimental data for making transgenic pigs with pig endogenous IGF1 gene. We constructed a skeletal muscle-specific expression vector using 5'- and 3'-regulatory regions of porcine skeletal α-actin gene...
February 22, 2018: Biochemical Genetics
https://www.readbyqxmd.com/read/29459701/imaging-of-electrical-activity-in-small-diameter-fibers-of-the-murine-peripheral-nerve-with-virally-delivered-gcamp6f
#17
Hans E Anderson, Arjun K Fontaine, John H Caldwell, Richard F Weir
Current neural interfaces are hampered by lack of specificity and selectivity for neural interrogation. A method that might improve these interfaces is an optical peripheral nerve interface which communicates with individual axons via optogenetic reporters. To determine the feasibility of such an interface, we delivered the genetically encoded calcium indicator GCaMP6f to the mouse peripheral nerve by intramuscular injection of adenoassociated viral vector (AAV1) under the control of the CAG (chicken beta actin- cytomegalovirus hybrid promoter)...
February 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29458530/sumoylation-of-ie2p86-is-required-for-efficient-autorepression-of-the-human-cytomegalovirus-major-immediate-early-promoter
#18
Nina Reuter, Anna Reichel, Anne-Charlotte Stilp, Myriam Scherer, Thomas Stamminger
The human cytomegalovirus (HCMV) IE2p86 protein is pivotal for coordinated regulation of viral gene expression. Besides functioning as a promiscuous transactivator, IE2p86 is also known to negatively regulate its own transcription. This occurs via direct binding of IE2p86 to a 14-bp palindromic DNA element located between the TATA box and the transcription start site of the major immediate-early promoter (MIEP), which is referred to as the cis repression signal (CRS). However, the exact mechanism of IE2p86-based autorepression is still unclear...
February 8, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29438402/haiku-new-paradigm-for-the-reverse-genetics-of-emerging-rna-viruses
#19
Thérèse Atieh, Miriam Diala El Ayoubi, Fabien Aubry, Stéphane Priet, Xavier de Lamballerie, Antoine Nougairède
Reverse genetics is key technology for producing wild-type and genetically modified viruses. The ISA (Infectious Subgenomic Amplicons) method is a recent versatile and user-friendly reverse genetics method to rescue RNA viruses. The main constraint of its canonic protocol was the requirement to produce (e.g., by DNA synthesis or fusion PCR) 5' and 3' modified genomic fragments encompassing the human cytomegalovirus promoter (pCMV) and the hepatitis delta virus ribozyme/simian virus 40 polyadenylation signal (HDR/SV40pA), respectively...
2018: PloS One
https://www.readbyqxmd.com/read/29437978/wdr5-facilitates-human-cytomegalovirus-replication-by-promoting-capsid-nuclear-egress
#20
Bo Yang, Xi-Juan Liu, Yongxuan Yao, Xuan Jiang, Xian-Zhang Wang, Hong Yang, Jin-Yan Sun, Yun Miao, Wei Wang, Zhen-Li Huang, Yanyi Wang, Qiyi Tang, Simon Rayner, William J Britt, Michael A McVoy, Min-Hua Luo, Fei Zhao
WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced infectious virus yield. However, WDR5 knockdown dramatically reduced infectious viral titers with only a small decrease in viral genome replication or gene expression...
February 7, 2018: Journal of Virology
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