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https://www.readbyqxmd.com/read/29208743/latency-associated-expression-of-human-cytomegalovirus-us28-attenuates-cell-signaling-pathways-to-maintain-latent-infection
#1
Benjamin A Krishna, Emma L Poole, Sarah E Jackson, Martine J Smit, Mark R Wills, John H Sinclair
Reactivation of human cytomegalovirus (HCMV) latent infection from early myeloid lineage cells constitutes a threat to immunocompromised or immune-suppressed individuals. Consequently, understanding the control of latency and reactivation to allow targeting and killing of latently infected cells could have far-reaching clinical benefits. US28 is one of the few viral genes that is expressed during latency and encodes a cell surface G protein-coupled receptor (GPCR), which, during lytic infection, is a constitutive cell-signaling activator...
December 5, 2017: MBio
https://www.readbyqxmd.com/read/29207540/herpesvirus-and-autophagy-all-right-everybody-be-cool-this-is-a-robbery
#2
REVIEW
Marion Lussignol, Audrey Esclatine
Autophagy is an essential vacuolar process of the cell, leading to lysosomal degradation and recycling of proteins and organelles, which is extremely important in maintaining homeostasis. Multiple roles have been now associated with autophagy, in particular a pro-survival role in nutrient starvation or in stressful environments, a role in life span extension, in development, or in innate and adaptive immunity. This cellular process can also take over microorganisms or viral proteins inside autophagosomes and degrade them directly in autolysosomes and is then called xenophagy and virophagy, respectively...
December 4, 2017: Viruses
https://www.readbyqxmd.com/read/29204649/aav2-mediated-transduction-of-the-mouse-retina-after-optic-nerve-injury
#3
Robert W Nickells, Heather M Schmitt, Margaret E Maes, Cassandra L Schlamp
Purpose: Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. Methods: Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29175632/intravenous-administration-of-the-adeno-associated-virus-php-b-capsid-fails-to-upregulate-transduction-efficiency-in-the-marmoset-brain
#4
Yasunori Matsuzaki, Ayumu Konno, Ryuta Mochizuki, Yoichiro Shinohara, Keisuke Nitta, Yukihiro Okada, Hirokazu Hirai
Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV9 containing seven amino acid insertions, results in a greater permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading to highly efficient and global transduction of the central nervous system (CNS). The present study aimed to examine whether the enhanced BBB penetrance of AAV-PHP.B observed in mice also occurs in non-human primates. Thus, a young adult (age, 1.6 years) and an old adult (age, 7...
November 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29160116/assessment-of-aav-serotype-tropism-in-human-retinal-explants
#5
Luke Aaron Wiley, Erin Burnight, Emily E Kaalberg, Chunhua Jiao, Megan J Riker, Jennifer A Halder, Meagan A Luse, Ian C Han, Stephen R Russell, Elliott H Sohn, Edwin Stone, Budd A Tucker, Robert F Mullins
Advances in the discovery of the causes of monogenic retinal disorders, combined with technologies for the delivery of DNA to the retina, offer enormous opportunities for the treatment of previously untreatable blinding diseases. However, for gene augmentation to be most effective, vectors that have the correct cell-type specificity are needed. While animal models are very useful, they often exhibit differences in retinal cell surface receptors compared to human retina. In this study, we evaluated the use of an ex vivo organotypic explant system to test the transduction efficiency and tropism of 7 different adeno-associated viral type 2 (AAV2) serotypes in human retina and retinal pigment epithelium-choroid: AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9, all driving expression of GFP under control of the cytomegalovirus promoter...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29159070/primary-cytomegalovirus-infection-in-immunocompetent-adults-in-the-united-states-a-case-series
#6
Nathanial Nolan, Umme-Aiman Halai, Hariharan Regunath, LPatrick Smith, Christian Rojas-Moreno, William Salzer
Primary Cytomegalovirus (CMV) infection is often not suspected as a cause of fever of unknown origin (FUO) in immune-competent adults. We present a case-series of symptomatic primary CMV infection in immunocompetent adults presenting as fever of unknown origin (FUO). All patients with CMV serology tested between November 2008 and June 2016 underwent chart review. Cases were defined as those between 18 and 65 years of age with documented fever and elevated serum anti-CMV IgM. Exclusion criteria were organ specific CMV disease, positive serum anti-EBV IgM, or presence of any immunocompromising condition...
2017: IDCases
https://www.readbyqxmd.com/read/29145435/functional-characterisation-of-filamentous-actin-probe-expression-in-neuronal-cells
#7
Shrujna Patel, Sandra Y Y Fok, Holly Stefen, Tamara Tomanić, Esmeralda Parić, Rosanna Herold, Merryn Brettle, Aleksandra Djordjevic, Thomas Fath
Genetically encoded filamentous actin probes, Lifeact, Utrophin and F-tractin, are used as tools to label the actin cytoskeleton. Recent evidence in several different cell types indicates that these probes can cause changes in filamentous actin dynamics, altering cell morphology and function. Although these probes are commonly used to visualise actin dynamics in neurons, their effects on axonal and dendritic morphology has not been systematically characterised. In this study, we quantitatively analysed the effect of Lifeact, Utrophin and F-tractin on neuronal morphogenesis in primary hippocampal neurons...
2017: PloS One
https://www.readbyqxmd.com/read/29138332/correction-for-perez-et-al-a-short-cis-acting-motif-in-the-m112-113-promoter-region-is-essential-for-ie3-to-activate-m112-113-gene-expression-and-is-important-for-murine-cytomegalovirus-replication
#8
Kareni J Perez, Francisco Puerta Martínez, Ruth Cosme-Cruz, Neysa M Perez-Crespo, Qiyi Tang
No abstract text is available yet for this article.
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29123113/talen-mediated-functional-correction-of-human-ipsc-derived-macrophages-in-context-of-hereditary-pulmonary-alveolar-proteinosis
#9
Alexandra Kuhn, Mania Ackermann, Claudio Mussolino, Toni Cathomen, Nico Lachmann, Thomas Moritz
Hereditary pulmonary alveolar proteinosis (herPAP) constitutes a rare, life threatening lung disease characterized by the inability of alveolar macrophages to clear the alveolar airspaces from surfactant phospholipids. On a molecular level, the disorder is defined by a defect in the CSF2RA gene coding for the GM-CSF receptor alpha-chain (CD116). As therapeutic options are limited, we currently pursue a cell and gene therapy approach aiming for the intrapulmonary transplantation of gene-corrected macrophages derived from herPAP-specific induced pluripotent stem cells (herPAP-iPSC) employing transcriptional activator-like effector nucleases (TALENs)...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121254/impact-of-donor-and-recipient-human-cytomegalovirus-status-on-kidney-transplantation
#10
Maciej Zielinski, Agnieszka Tarasewicz, Hanna Zielinska, Magdalena Jankowska, Grazyna Moszkowska, Alicja Debska-Slizien, Boleslaw Rutkowski, Piotr Trzonkowski
Human cytomegalovirus (HCMV) is considered to be a major pathogen that affects the outcome of solid organ transplantation. Both recipient and donor may be HCMV positive, therefore HCMV reinfection is possible after transplantation. However, little is known how cytomegalovirus transmitted from an infected donor to an infected recipient modulates the recipient's already suppressed immunity, and what the clinical consequences are. To investigate these issues, 52 kidney recipients were followed up for two years after transplantation...
November 7, 2017: International Immunology
https://www.readbyqxmd.com/read/29115546/influence-of-the-twist-gene-on-the-invasion-and-metastasis-of-colon-cancer
#11
Duowei Wang, Bikash Rai, Feng Qi, Tong Liu, Jinmiao Wang, Xiaodong Wang, Bozhao Ma
The present study investigated the role of the Twist gene in epithelial-mesenchymal transition (EMT) and its effects on the invasion and metastasis of malignant tumors. In vitro, we transfected SW480, HCT116 and HT29 cells with recombinant plasmids, pTracer-CMV/BSD-Twist and pGenesil1.2-Twist-shRNA, to influence expression of Twist. The transfection efficacy of the plasmids in the cell lines was confirmed by flow cytometry. The relative mRNA and protein expression levels of Twist, E-cadherin and vimentin in the transfected cells were detected by RT-PCR and western blotting, respectively...
November 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29114247/elusive-role-of-the-cd94-nkg2c-nk-cell-receptor-in-the-response-to-cytomegalovirus-novel-experimental-observations-in-a-reporter-cell-system
#12
Aldi Pupuleku, Marcel Costa-García, Domènec Farré, Hartmut Hengel, Ana Angulo, Aura Muntasell, Miguel López-Botet
Human cytomegalovirus (HCMV) infection promotes the differentiation and persistent expansion of a mature NK cell subset, which displays high surface levels of the activating CD94/NKG2C NK cell receptor, together with additional distinctive phenotypic and functional features. The mechanisms underlying the development of adaptive NK cells remain uncertain but some observations support the involvement of a cognate interaction of CD94/NKG2C with ligand(s) displayed by HCMV-infected cells. To approach this issue, the heterodimer and its adaptor (DAP12) were expressed in the human Jurkat leukemia T cell line; signaling was detected by transfection of a reporter plasmid encoding for Luciferase (Luc) under NFAT/AP1-dependent control...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29108855/hiv-patients-healthy-aging-and-transplant-recipients-can-reveal-the-hidden-footprints-of-cmv
#13
REVIEW
Shelley Waters, Emily Brook, Silvia Lee, Riwanti Estiasari, Ibnu Ariyanto, Patricia Price
Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to a repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the "clinical footprints" as immunopathologies triggered by CMV that develop over many years...
November 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#14
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches (Olson et al. 2000) necessitates the development of alternative testing approaches. Body of evidence associates DILI with the induction of stress-response genes in the liver cells (Yuan and Kaplowitz 2013). Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29105189/cyclophosphamide-induced-tolerance-in-kidney-transplantation-avoids-long-term-immunosuppressive-therapy
#15
REVIEW
Ario Takeuchi, Koji Kato, Koichi Akashi, Masatoshi Eto
There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of T cells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation...
November 3, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29093653/comparison-of-the-commercial-quantiferon-cmv-and-overlapping-peptide-based-elispot-assays-for-predicting-cmv-infection-in-kidney-transplant-recipients
#16
Ji-Soo Kwon, Taeeun Kim, Sun-Mi Kim, Heungsup Sung, Sung Shin, Young Hoon Kim, Eui-Cheol Shin, Sung-Han Kim, Duck Jong Han
Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Tests for CMV-specific T cell responses have been proposed to change the current risk stratification strategy using CMV assays. We evaluated the usefulness of pre-transplant CMV-specific T cell assays in kidney transplant (KT) candidates for predicting the development of CMV infection after transplantation comparing the results of the overlapping peptides (OLPs)-based enzyme-linked immunospot (ELISPOT) assay and the commercial QuantiFERON-CMV assay...
October 2017: Immune Network
https://www.readbyqxmd.com/read/29082387/modulation-of-the-nf%C3%AE%C2%BAb-signalling-pathway-by-human-cytomegalovirus
#17
Meaghan H Hancock, Jay A Nelson
Many viruses trigger innate and adaptive immune responses and must circumvent the negative consequences to successfully establish infection in their hosts. Human Cytomegalovirus (HCMV) is no exception, and devotes a significant portion of its coding capacity to genes involved in immune evasion. Activation of the NFκB signalling pathway by viral binding and entry results in induction of antiviral and pro-inflammatory genes that have significant negative effects on HCMV infection. However, NFκB signalling stimulates transcription from the Major Immediate Early Promoter (MIEP) and pro-inflammatory signalling is crucial for cellular differentiation and viral reactivation from latency...
August 2017: Virology: Current Research
https://www.readbyqxmd.com/read/29079770/ocular-antigen-does-not-cause-disease-unless-presented-in-the-context-of-inflammation
#18
Valentina Voigt, Matthew E Wikstrom, Jelena M Kezic, Iona S Schuster, Peter Fleming, Kimmo Makinen, Stephen R Daley, Christopher E Andoniou, Mariapia A Degli-Esposti, John V Forrester
Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29076066/recombinant-baculovirus-based-vaccine-expressing-m2-protein-induces-protective-cd8-t-cell-immunity-against-respiratory-syncytial-virus-infection
#19
Jeong-Yoon Lee, Jun Chang
Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract disease in infants, young children, immunocompromised individuals, and the elderly. However, despite ongoing efforts to develop an RSV vaccine, there is still no authorized RSV vaccine for humans. Baculovirus has attracted attention as a vaccine vector because of its ability to induce a high level of humoral and cellular immunity, low cytotoxicity against various antigens, and biological safety for humans. In this study, we constructed a recombinant baculovirus- based vaccine expressing the M2 protein of RSV under the control of cytomegalovirus promoter (Bac_RSVM2) to induce CD8(+) T-cell responses which play an important role in viral clearance, and investigated its protective efficacy against RSV infection...
November 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/29072334/protective-efficacy-of-an-il-12-expressing-baculoviral-malaria-vaccine
#20
Mitsuhiro Iyori, Andrew M Blagborough, Katarzyna A Sala, Hidesato Nishiura, Kentaro Takagi, Shigeto Yoshida
Interleukin-12 (IL-12) plays an important role in antigen-specific adaptive immunity against Plasmodium sporozoites, and this requirement allows for a new approach to developing an effective malaria vaccine. In the present study, we examined whether IL-12 could enhance protective efficacy of a baculovirus-based malaria vaccine. For this aim, a baculoviral vector expressing murine IL-12 (mIL-12) under the control of CMV promoter (BES-mIL-12-Spider) and a baculoviral vector expressing Plasmodium falciparum circumsporozoite protein (PfCSP) with post-transcriptional regulatory element of woodchuck hepatitis virus (BDES-sPfCSP2-WPRE-Spider) were generated...
October 26, 2017: Parasite Immunology
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