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https://www.readbyqxmd.com/read/28096485/murine-cytomegalovirus-deubiquitinase-regulates-viral-chemokine-levels-to-control-inflammation-and-pathogenesis
#1
Adam T Hilterbrand, Daniel R Boutz, Edward M Marcotte, Jason W Upton
: Maintaining control over inflammatory processes represents a paradox for viral pathogens. Although many viruses induce host inflammatory responses to facilitate infection, control is necessary to avoid overactivation. One way is through the manipulation of proinflammatory chemokine levels, both host and viral. Murine cytomegalovirus (MCMV), a model betaherpesvirus, encodes a viral C-C chemokine, MCK2, which promotes host inflammatory responses and incorporates into virions to facilitate viral dissemination...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096054/glycogen-storage-disease-type-ia-mice-with-less-than-2-of-normal-hepatic-glucose-6-phosphatase-%C3%AE-activity-restored-are-at-risk-of-developing-hepatic-tumors
#2
Goo-Young Kim, Young Mok Lee, Joon Hyun Kwon, Jun-Ho Cho, Chi-Jiunn Pan, Matthew F Starost, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown...
January 10, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28095500/senp7-potentiates-cgas-activation-by-relieving-sumo-mediated-inhibition-of-cytosolic-dna-sensing
#3
Ye Cui, Huansha Yu, Xin Zheng, Rui Peng, Qiang Wang, Yi Zhou, Rui Wang, Jiehua Wang, Bo Qu, Nan Shen, Qiang Guo, Xing Liu, Chen Wang
Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2'3'-cGAMP that activates the stimulator of interferon genes (STING) signaling. How the cGAS activity is modulated remains largely unknown. Here, we demonstrate that sentrin/SUMO-specific protease 7 (SENP7) interacted with and potentiated cGAS activation. The small ubiquitin-like modifier (SUMO) was conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppressed its DNA-binding, oligomerization and nucleotidyl-transferase activities...
January 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28095439/intracranial-injection-of-dengue-virus-induces-interferon-stimulated-genes-and-cd8-t-cell-infiltration-by-sphingosine-kinase-1-independent-pathways
#4
Wisam H Al-Shujairi, Jennifer N Clarke, Lorena T Davies, Mohammed Alsharifi, Stuart M Pitson, Jillian M Carr
We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28094877/hypothalamus-specific-re-introduction-of-snord116-into-otherwise-snord116-deficient-mice-increased-energy-expenditure
#5
Y Qi, L Purtell, M Fu, L Zhang, S Zolotukhin, L Campbell, H Herzog
The Snord116 gene cluster has been recognized as a critical contributor to the Prader-Willi Syndrome (PWS) with mice lacking Snord116 displaying many classical PWS phenotypes including low postnatal body weight, reduced bone mass and increased food intake. However, these mice do not develop obesity due to increased energy expenditure. To understand the physiological function of Snord116 better and potentially rescue the altered metabolism of Snord116(-/-) mice, we used an adeno-associated viral (AAV) approach to reintroduce the Snord116 gene product into the hypothalamus in Snord116(-/-) mice at different ages...
January 17, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28094802/extrinsic-mavs-signaling-is-critical-for-treg-maintenance-of-foxp3-expression-following-acute-flavivirus-infection
#6
Andreia Da Costa, Esteban Garza, Jessica B Graham, Jessica L Swarts, Andrew G Soerens, Michael Gale, Jennifer M Lund
Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding of the key mediators of an effective anti-viral response. We previously demonstrated that WNV infection of mice deficient in mitochondrial antiviral-signaling protein (MAVS), the signaling adaptor for RNA helicases such as RIG-I, resulted in increased death and dysregulated immunity, which correlated with a failure of Treg expansion following infection. Thus, we sought to determine if intrinsic MAVS signaling is required for participation of Tregs in anti-WNV immunity...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094780/rapid-acquisition-of-polymorphic-virulence-markers-during-adaptation-of-highly-pathogenic-avian-influenza-h5n8-virus-in-the-mouse
#7
Won-Suk Choi, Yun Hee Baek, Jin Jung Kwon, Ju Hwan Jeong, Su-Jin Park, Young-Il Kim, Sun-Woo Yoon, Jungwon Hwang, Myung Hee Kim, Chul-Joong Kim, Richard J Webby, Young Ki Choi, Min-Suk Song
Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094330/inhibition-of-influenza-a-virus-infection-by-fucoidan-targeting-viral-neuraminidase-and-cellular-egfr-pathway
#8
Wei Wang, Jiandong Wu, Xiaoshuang Zhang, Cui Hao, Xiaoliang Zhao, Guangling Jiao, Xindi Shan, Wenjing Tai, Guangli Yu
Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidan in vitro and in vivo. The results showed that a fucoidan KW derived from brown algae Kjellmaniella crassifolia effectively blocked IAV infection in vitro with low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092946/carcinogenesis-of-the-oral-cavity-environmental-causes-and-potential-prevention-by-black-raspberry
#9
Karam El-Bayoumy, Kun-Ming Chen, Shang-Min Zhang, Yuan-Wan Sun, Shantu Amin, Gary Stoner, Joseph B Guttenplan
Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092646/ex-vivo-nonviral-gene-delivery-of-%C3%AE-opioid-receptor-to-attenuate-cancer-induced-pain
#10
Seiichi Yamano, Chi T Viet, Dongmin Dang, Jisen Dai, Shigeru Hanatani, Tadahiro Takayama, Hironori Kasai, Kentaro Imamura, Ron Campbell, Yi Ye, John C Dolan, William Myung Kwon, Stefan D Schneider, Brian L Schmidt
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells...
February 2017: Pain
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-il-23-mediated-protection-against-cona-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#11
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδT cells and liver damage in patients with HBV. However, whether γδT cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using hepatitis B virus transgenic (HBs-Tg) and HBs-Tg-TCRδ(-/-) mice, we found that mice genetically deficient in γδT cells exhibited more severe liver damage upon ConcanavalinA (ConA) treatment, as indicated by substantially higher serum alanine aminotransferase (ALT) levels, further elevated IFN-γ levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28090751/a-safety-checkpoint-to-eliminate-cancer-risk-of-the-immune-evasive-cells-derived-from-human-embryonic-stem-cells
#12
Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the co-expression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28089770/structural-pierce-into-molecular-mechanism-underlying-clostridium-perfringens-epsilon-toxin-function
#13
Saeed Khalili, Abolfazl Jahangiri, Zahra Sadat Hashemi, Bahman Khalesi, Meysam Mardsoltani, Jafar Amani
Epsilon toxin of the Clostridium perfringens garnered a lot of attention due to its potential for toxicity in humans, extreme potency for cytotoxicity in mice and lack of any approved therapeutics prescribed for human. However, the intricacies of the Epsilon toxin action mechanism are yet to be understood. In this regard, various in silico tools have been exploited to model and refine the 3D structure of the toxin and its two receptors. The receptor proteins were embedded into designed lipid membranes within an aqueous and ionized environment...
January 12, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28089546/expression-of-interleukin-6-by-a-recombinant-rabies-virus-enhances-its-immunogenicity-as-a-potential-vaccine
#14
Jun Luo, Boyue Zhang, Yuting Wu, Qin Tian, Jing Zhao, Ziyu Lyu, Qiong Zhang, Mingzhu Mei, Yongwen Luo, Xiaofeng Guo
Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain...
January 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28088781/mir-30c-5p-ameliorates-hepatic-steatosis-in-leptin-receptor-deficient-db-db-mice-via-down-regulating-fasn
#15
Jiahui Fan, Huaping Li, Xiang Nie, Zhongwei Yin, Yanru Zhao, Chen Chen, Dao Wen Wang
Approximately 15-40% of the general adult population suffers from non-alcoholic fatty liver disease (NAFLD) worldwide. However, no drug is currently licensed for its treatment. In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#16
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#17
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28087313/an-m2-v27a-channel-blocker-demonstrates-potent-in-vitro-and-in-vivo-antiviral-activities-against-amantadine-sensitive-and-resistant-influenza-a-viruses
#18
Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F Smee, William F DeGrado, Jun Wang
Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target...
January 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28086957/regulatory-t-cells-and-il10-suppress-pulmonary-host-defense-during-early-life-exposure-to-radical-containing-combustion-derived-ultrafine-particulate-matter
#19
Sridhar Jaligama, Jordy Saravia, Dahui You, Nikki Yadav, Greg I Lee, Bishwas Shrestha, Stephania A Cormier
BACKGROUND: Exposure to elevated levels of particulate matter (PM) is associated with increased risk of morbidity and mortality due to respiratory tract viral infections in infants. Recent identification of environmentally persistent free radicals (EPFRs) in the PM from a variety of combustion sources suggests its role in the enhancement of disease severity of lower respiratory tract infections (LRTI). Our previous studies demonstrated that acute exposure to EPFRs induces pulmonary immunosuppression allowing for enhanced influenza disease severity...
January 13, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28081442/mapping-and-role-of-the-cd8-t-cell-response-during-primary-zika-virus-infection-in-mice
#20
Annie Elong Ngono, Edward A Vizcarra, William W Tang, Nicholas Sheets, Yunichel Joo, Kenneth Kim, Matthew J Gorman, Michael S Diamond, Sujan Shresta
CD8(+) T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8(+) T cell response in ZIKV-infected LysMCre(+)IFNAR(fl/fl) C57BL/6 (H-2(b)) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8(+) T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated. CD8(+) T cells from infected mice were polyfunctional and mediated cytotoxicity...
January 11, 2017: Cell Host & Microbe
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