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Darin K Edwards, Edith Jasny, Heesik Yoon, Nigel Horscroft, Brian Schanen, Tanya Geter, Mariola Fotin-Mleczek, Benjamin Petsch, Vaughan Wittman
BACKGROUND: Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. METHODS: In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model...
January 3, 2017: Journal of Translational Medicine
Kai Zheng, Yingchun Jiang, Zhendan He, Kaio Kitazato, Yifei Wang
AbstractHistone deacetylase 6 (HDAC6) is an unique cytoplasmic deacetylase that regulates various important biological processes via preventing protein aggregation and deacetylating different non-histone substrates including tubulin, heat shock protein 90 (Hsp90), cortactin, retinoic acid inducible gene I (RIG-1) and β-catenin. Growing evidences have indicated a dual role for HDAC6 in viral infection and pathogenesis: HDAC6 may represent a host defense mechanism against viral infection through modulating microtubule, triggering antiviral immune response and stimulating protective autophagy, or it may be hijacked by the virus to enhance proinflammatory response...
December 12, 2016: Journal of General Virology
Ghayathri Balasundaram, Timothy Weixin Kwang, Shu Wang
Recombinant insect baculoviral vectors efficiently transduce several types of cells in the brain and can possibly be used in gene therapy for brain disorders. However, together with contaminating insect cell proteins, they trigger immune responses that might damage host brain cells. To substantially reduce unwanted immune responses due to the insect cell impurities, we purified and concentrated baculoviral vectors by combining an ion-exchange membrane chromatography method with high-speed centrifugation and demonstrated reduced immune responses of the vector preparations in the mouse brain...
November 2, 2016: Journal of Neurochemistry
Vivekanandhan Aravindhan, Haridoss Madhumitha
Globally, noncommunicable chronic diseases such as Type-2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD) are posing a major threat to the world. T2DM is known to potentiate CAD which had led to the coining of a new clinical entity named diabetic CAD (DM-CAD), leading to excessive morbidity and mortality. The synergistic interaction between these two comorbidities is through sterile inflammation which is now being addressed as metabolic inflammation or metainflammation, which plays a pivotal role during both early and late stages of T2DM and also serves as a link between T2DM and CAD...
2016: Journal of Diabetes Research
Manisha Priyam, Mamta Tripathy, Umesh Rai, Soma Mondal Ghorai
Reptiles remain a deprived class in the area of genomic and molecular resources for the vertebrate classes. The transition of squamates from aquatic to terrestrial mode of life caused profound changes in their immune system to combat the altered variety of pathogens on land. The current study aims at delineating the evolution of defence mechanisms in wall lizard, Hemidactylus flaviviridis, by exploring its immunome. De novo sequencing of splenic transcriptome from wall lizard on the Illumina Hi-Seq platform generated 258,128 unique transcripts with an average GC content of 45%...
April 2016: Veterinary Immunology and Immunopathology
Rose Yvonne Reins, Hasna Baidouri, Alison Marie McDermott
PURPOSE: Vitamin D is recognized to be an important modulator of the immune system. In the eye, studies have shown that deficiencies and genetic differences in vitamin D-related genes have a significant impact on the development of various ocular diseases. Our current study examines the ability of human corneal epithelial cells (HCEC) to activate vitamin D and the effect of vitamin D treatment on antimicrobial peptide production and cytokine modulation during inflammation, with the ultimate goal of using vitamin D therapeutically for corneal inflammation...
December 2015: Investigative Ophthalmology & Visual Science
P Drayton, B W Morgan, M C Davies, G E B Giddins, A W Miles
: Silicone finger arthroplasties are used widely, especially for metacarpophalangeal joint replacement in patients with inflammatory arthritis. Implant failure is well recognized. The rates of failure in vivo differ substantially from experience in vivo. One cause of failure is felt to be post-operative ulnar deviation. The aim of our study was to test the effect of ulnar deviation testing on silicone finger implants. We tested 12 implants in three groups of four implants. The implants were submerged in a bath of Ringer's solution at 370 °C throughout the experiment and tested in a rig held in 0°, 10° and 20° deviation...
November 2016: Journal of Hand Surgery, European Volume
A Pretorius, F E Faber, M van Kleef
Development of African horsesickness (AHS) subunit vaccines will have to include a rational approach that uses knowledge of how the virus interacts with the host immune system. The global in vivo immune response induced by attenuated AHSV serotype 4 in horses was characterised using transcriptome sequencing. PBMC were collected with 24h intervals for four days after inoculation and four days after a second boost, 21 days later. Transcriptome data were normalised to the day 0 naïve transcriptome and up- or down-regulated immune genes identified using the CLC workbench...
February 2016: Immunobiology
Sanna M Mäkelä, Pamela Österlund, Veera Westenius, Sinikka Latvala, Michael S Diamond, Michael Gale, Ilkka Julkunen
UNLABELLED: Influenza B virus causes annual epidemics and, along with influenza A virus, accounts for substantial disease and economic burden throughout the world. Influenza B virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza A virus. Influenza B virus has been less studied than influenza A virus, and thus, a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions...
December 2015: Journal of Virology
Alexander S Jureka, Alex B Kleinpeter, Gabriel Cornilescu, Claudia C Cornilescu, Chad M Petit
The influenza non-structural protein 1 (NS1) plays a critical role in antagonizing the innate immune response to infection. One interaction that facilitates this function is between NS1 and RIG-I, one of the main sensors of influenza virus infection. While NS1 and RIG-I are known to interact, it is currently unclear whether this interaction is direct or if it is mediated by other biomolecules. Here we demonstrate a direct, strain-dependent interaction between the NS1 RNA binding domain (NS1(RBD)) of the influenza A/Brevig Mission/1918 H1N1 (1918(H1N1)) virus and the second caspase activation and recruitment domain of RIG-I...
November 3, 2015: Structure
Xian-Lin Wu, Yu-Hong Luo, Jia Chen, Bin Yu, Kang-Li Liu, Jin-Xiong He, Su-Hong Lu, Jie-Xing Li, Sha Wu, Zhen-You Jiang, Xiao-Yin Chen
Over the past few decades, climate warming has caused profound changes in our living environment, and human diseases, including infectious diseases, have also been influenced by these changes. However, it remains unclear if a warm-wet climate can influence the infectivity of influenza and result in influenza pandemics. This study focused on observations of how the hydrothermal environment influences the infectivity of the influenza virus and the resulting immunoreactions of the infected mice. We used a manual climatic box to establish the following 3 environments with different temperatures and humidity: normal environment (T: 24 ± 1°C, RH: 50% ± 4%), wet environment (T: 24 ± 1 °C, RH: 95% ± 4%) and warm-wet environment (T: 33 ± 1 °C, RH: 95% ± 4%), and the mice were fed and maintained in these 3 different environments...
2015: Human Vaccines & Immunotherapeutics
Xiaoqing Zhang, Haiyang Yu, Jun Zhao, Xiuqing Li, Jiada Li, Jiantai He, Zanxian Xia, Jinfeng Zhao
Inhibitor of nuclear factor kappa-B kinase Epsilon (IKKϵ) is an IKK-related kinase. Despite it was originally discovered as a kinase functionally related to TBK-1, studies entailing gene knockout mouse demonstrated that IKKϵ is dispensable for interferon induction by viral infection. In this study, we report that IKKϵ directly phosphorylates a key serine residue within the RNA-binding domain of RIG-I (retinoic acid-inducible gene 1) to inhibit RIG-I-mediate innate immune signaling. Using IKKϵ-deficient MEFs, we found that loss of IKKϵ resulted in increased cytokine production in response to the activation of cytosolic sensors...
April 2016: Journal of Medical Virology
Martin Zens, Philipp Niemeyer, Anke Bernstein, Matthias J Feucht, Jan Kühle, Norbert P Südkamp, Peter Woias, Herrmann O Mayr
PURPOSE: Knee joint laxities are observed in patients after severe trauma to the joint, resulting in ligament tears. Specifically, injuries to the anterior cruciate ligament may cause a significant instability. The degree of these laxities is essential in diagnostics and may affect which treatment option is suggested. METHODS: Polydimethylsiloxane (PDMS) strain gauges are proposed as a non-invasive, highly accurate and easy-to-use measurement method to quantify anterolateral and rotational laxities of the knee joint during active and passive motion...
October 2015: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
Omesh Kumar Bharti, Shampur Narayan Madhusudana, Pyare Lal Gaunta, Ashwin Yajaman Belludi
Presently the dose of rabies immunoglobulin (RIG) which is an integral part of rabies post exposure prophylaxis (PEP) is calculated based on body weight though the recommendation is to infiltrate the wound(s). This practice demands large quantities of RIG which may be unaffordable to many patients. In this background, we conducted this study to know if the quantity and cost of RIG can be reduced by restricting passive immunization to local infiltration alone and avoiding systemic intramuscular administration based on the available scientific evidence...
March 3, 2016: Human Vaccines & Immunotherapeutics
Alison Kell, Mark Stoddard, Hui Li, Joe Marcotrigiano, George M Shaw, Michael Gale
UNLABELLED: Despite the introduction of direct-acting antiviral (DAA) drugs against hepatitis C virus (HCV), infection remains a major public health concern because DAA therapeutics do not prevent reinfection and patients can still progress to chronic liver disease. Chronic HCV infection is supported by a variety of viral immune evasion strategies, but, remarkably, 20% to 30% of acute infections spontaneously clear prior to development of adaptive immune responses, thus implicating innate immunity in resolving acute HCV infection...
November 2015: Journal of Virology
Liyan Cao, Xuying Ge, Yu Gao, Georg Herrler, Yudong Ren, Xiaofeng Ren, Guangxing Li
BACKGROUND: The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species...
2015: Virology Journal
Tianle Gu, Youliang Rao, Jianguo Su, Chunrong Yang, Xiaohui Chen, Lijun Chen, Nana Yan
Melanoma differentiation-associated gene 5 (MDA5) is a member of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family which can initiate type I IFN expression in response to RNA virus infection. In this study, we constructed six mutants of Ctenopharyngodon idella MDA5 (CiMAD5) overexpression plasmids and generated stable transfected C. idella kidney (CIK) cell lines to study the function of different domains of CiMAD5. After ploy(I:C) stimulation, the downstream genes of CiMDA5 in transfected cells was repressed...
October 2015: Fish & Shellfish Immunology
Ling Wang, Guangyu Li, Zhi Q Yao, Jonathan P Moorman, Shunbin Ning
MicroRNAs (miRNAs) function as key regulators in immune responses and cancer development. In the contexts of infection with oncogenic viruses, miRNAs are engaged in viral persistence, latency establishment and maintenance, and oncogenesis. In this review, we summarize the potential roles and mechanisms of viral and cellular miRNAs in the host-pathogen interactions during infection with selected tumor viruses and HIV, which include (i) repressing viral replication and facilitating latency establishment by targeting viral transcripts, (ii) evading innate and adaptive immune responses via toll-like receptors, RIG-I-like receptors, T-cell receptor, and B-cell receptor pathways by targeting signaling molecules such as TRAF6, IRAK1, IKKε, and MyD88, as well as downstream targets including regulatory cytokines such as tumor necrosis factor α, interferon γ, interleukin 10, and transforming growth factor β, (iii) antagonizing intrinsic and extrinsic apoptosis pathways by targeting pro-apoptotic or anti-apoptotic gene transcripts such as the Bcl-2 family and caspase-3, (iv) modulating cell proliferation and survival through regulation of the Wnt, PI3K/Akt, Erk/MAPK, and Jak/STAT signaling pathways, as well as the signaling pathways triggered by viral oncoproteins such as Epstein-Barr Virus LMP1, by targeting Wnt-inhibiting factor 1, SHIP, pTEN, and SOCSs, and (v) regulating cell cycle progression by targeting cell cycle inhibitors such as p21/WAF1 and p27/KIP1...
September 2015: Reviews in Medical Virology
Alysson H Blaine, Domingo Miranzo-Navarro, Lee K Campbell, Jerry R Aldridge, Robert G Webster, Katharine E Magor
Wild waterfowl, including mallard ducks, are the natural reservoir of avian influenza A virus and they are resistant to strains that would cause fatal infection in chickens. Here we investigate potential involvement of TRIM proteins in the differential response of ducks and chickens to influenza. We examine a cluster of TRIM genes located on a single scaffold in the duck genome, which is a conserved synteny group with a TRIM cluster located in the extended MHC region in chickens and turkeys. We note a TRIM27-like gene is present in ducks, and absent in chickens and turkeys...
October 2015: Molecular Immunology
Milena Nasi, Sara De Biasi, Elena Bianchini, Margherita Digaetano, Marcello Pinti, Lara Gibellini, Simone Pecorini, Gianluca Carnevale, Giovanni Guaraldi, Vanni Borghi, Cristina Mussini, Andrea Cossarizza
OBJECTIVE: Few studies have investigated the importance of different components of the inflammasome system and of innate mitochondrial sensing (IMS) pathways in HIV infection and its treatment. We analysed the expression of several components of the inflammasome and of the IMS in HIV-positive patients taking successful combination antiretroviral therapy (cART). METHODS: We enrolled 20 HIV-positive patients under cART, who achieved viral suppression since at least 10 months and 20 age and sex-matched healthy donors...
September 24, 2015: AIDS
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