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https://www.readbyqxmd.com/read/29908447/fas-activity-mediates-airway-inflammation-during-mouse-adenovirus-type-1-respiratory-infection
#1
Laura J Adkins, Caitlyn T Molloy, Jason B Weinberg
CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice...
June 13, 2018: Virology
https://www.readbyqxmd.com/read/29908240/the-gabaergic-gudden-s-dorsal-tegmental-nucleus-a-new-relay-for-serotonergic-regulation-of-sleep-wake-behavior-in-the-mouse
#2
Marine Chazalon, Sylvie Dumas, Jean-François Bernard, Iman Sahly, François Tronche, Alban de Kerchove d'Exaerde, Michel Hamon, Joëlle Adrien, Véronique Fabre, Patricia Bonnavion
Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1A R) in the brainstem, a major wake/REM sleep regulatory center. However, the neuroanatomical substrate through which 5-HT1A R influence sleep remains elusive. We therefore investigated whether a brainstem structure containing a high density of 5-HT1A R mRNA, the GABAergic Gudden's dorsal tegmental nucleus (DTg), may contribute to 5-HT-mediated regulatory mechanisms of sleep-wake stages...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29907765/dual-functional-peptide-with-defective-interfering-genes-effectively-protects-mice-against-avian-and-seasonal-influenza
#3
Hanjun Zhao, Kelvin K W To, Hin Chu, Qiulu Ding, Xiaoyu Zhao, Cun Li, Huiping Shuai, Shuofeng Yuan, Jie Zhou, Kin-Hang Kok, Shibo Jiang, Kwok-Yung Yuen
Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification...
June 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29907232/intramuscular-e-selectin-adeno-associated-virus-gene-therapy-promotes-wound-healing-in-an-ischemic-mouse-model
#4
Punam P Parikh, Roberta M Lassance-Soares, Hongwei Shao, Manuela M Regueiro, Yan Li, Zhao-Jun Liu, Omaida C Velazquez
BACKGROUND: Poor wound healing in critical limb ischemia (CLI) is attributed to impaired neovascularization and reperfusion. Optimizing the ischemic wound with adhesion molecules that enhance stem cell homing may revolutionize treatment. The purpose of this study is to test the efficacy of adhesion molecule E-selectin on wound healing in an ischemic mouse wound. METHODS: Adult FVB/NJ mice underwent unilateral femoral artery and vein ligation to induce CLI. A 4-mm punch biopsy wound was created on the anterior thigh to simulate ischemic wounds...
August 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29906396/synthesis-and-evaluation-of-n-phenyl-3-sulfamoyl-benzamide-derivatives-as-capsid-assembly-modulators-inhibiting-hepatitis-b-virus-hbv
#5
Koen Vandyck, Geert Rombouts, Bart Stoops, Abdellah Tahri, Ann Vos, Wim Verschueren, Yiming Wu, Jingmei Yang, Fuliang Hou, Bing Huang, Karen Vergauwen, Pascale Dehertogh, Jan-Martin Berke, Pierre Jean Marie Bernard Raboisson
Small molecule induced Hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts towards the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice, resulted in a 2.77 log reduction of the HBV DNA viral load.
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29906223/new-mouse-model-of-pulmonary-hypertension-induced-by-respiratory-syncytial-virus-bronchiolitis
#6
Dai Kimura, Jordy Saravia, Sridhar Jaligama, Isabella McNamara, Luan D Vu, Ryan D Sullivan, Salvatore Mancarella, Dahui You, Stephania A Cormier
Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of this study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age, and then re-infected 4 weeks later. Serum free medium was administered to age-matched mice as control...
June 15, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29905053/-effect-of-human-adipose-derived-stem-cells-on-pressure-ulcer-healing-in-mouse
#7
Chengliang Deng, Zhiyuan Liu, Yuanzhen Yao, Ruichi Liu, Zairong Wei, Dali Wang
Objective: To investigate the effect of human adipose-derived stem cells (hADSCs) on pressure ulcers in mouse. Methods: The subcutaneous adipose tissue from voluntary donation was harvested. Then the hADSCs were isolated and cultured by mechanical isolation combined with typeⅠcollagenase digestion. The 3rd generation cells were identified by osteogenic, adipogenic, chondrogenic differentiations and flow cytometry. The platelet rich plasma (PRP) from peripheral blood donated by healthy volunteers was prepared by centrifugation...
June 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/29902992/cancer-immunoprevention-from-mice-to-early-clinical-trials
#8
REVIEW
Arianna Palladini, Lorena Landuzzi, Pier-Luigi Lollini, Patrizia Nanni
Cancer immunoprevention is based on the fact that a functioning immune system controls tumor onset and development in humans and animals, thus leading to the idea that the enhancement of immune responses in healthy individuals could effectively reduce cancer risk later in life. Successful primary immunoprevention of tumors caused by hepatitis B and papilloma viruses is already implemented at the population level with specific vaccines. The immunoprevention of human tumors unrelated to infectious agents is an outstanding challenge...
June 15, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29902727/live-attenuated-bivalent-measles-virus-derived-vaccines-targeting-middle-east-respiratory-syndrome-coronavirus-induce-robust-and-multifunctional-t-cell-responses-against-both-viruses-in-an-appropriate-mouse-model
#9
Bianca S Bodmer, Anna H Fiedler, Jan R H Hanauer, Steffen Prüfer, Michael D Mühlebach
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MVvac2 -MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MVvac2 -MERS-S(H) or novel MVvac2 -MERS-N were further characterized...
June 11, 2018: Virology
https://www.readbyqxmd.com/read/29902449/timing-of-gestational-exposure-to-zika-virus-is-associated-with-postnatal-growth-restriction-in-a-murine-model
#10
Gregory C Valentine, Maxim D Seferovic, Stephanie W Fowler, Angela M Major, Rodion Gorchakov, Rebecca Berry, Alton G Swennes, Kristy O Murray, Melissa A Suter, Kjersti M Aagaard
BACKGROUND: Vertical transmission of Zika virus (ZIKV) leads to infection of neuroprogenitor cells and destruction of brain parenchyma. Recent evidence suggests that the timing of infection as well as host factors may affect vertical transmission. As a result, congenital ZIKV infection may only become clinically apparent in the postnatal period. OBJECTIVES: We sought to develop an outbred mouse model of ZIKV vertical transmission to determine if the timing of gestational ZIKV exposure yields phenotypic differences at birth and through adolescence...
June 11, 2018: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29901418/systemic-delivery-of-aavb1-gaa-clears-glycogen-and-prolongs-survival-in-a-mouse-model-of-pompe-disease
#11
Allison May Keeler, Marina Zieger, Sophia Todeasa, Angela Mccall, Jennifer Gifford, Samantha Bircsak, Sourav Roy Choudhury, Barry J Byrne, Miguel Sena-Esteves, Mai K ElMallah
Pompe disease is an autosomal recessive glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption in muscle and central nervous system (CNS). Adeno-associated virus (AAV) gene therapy is ideal for Pompe disease since a single systemic injection may correct both muscle and CNS pathologies. Using the Pompe mouse, we sought to explore if AAVB1, a newly engineered vector with a high affinity for muscle and CNS, reduces systemic weakness and improves survival in adult mice...
June 14, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29900416/mir-155-induction-is-a-marker-of-murine-norovirus-infection-but-does-not-contribute-to-control-of-replication-in-vivo
#12
Lucy Thorne, Jia Lu, Yasmin Chaudhry, Ian Goodfellow
Background: Due to their role in fine-tuning cellular protein expression, microRNAs both promote viral replication and contribute to antiviral responses, for a range of viruses. The interactions between norovirus and the microRNA machinery have not yet been studied. Here, we investigated the changes that occur in microRNA expression during murine norovirus (MNV) infection. Methods: Using RT-qPCR-based arrays, we analysed changes in miRNA expression during infection with the acute strain MNV-1 in two permissive cell lines, a murine macrophage cell line, RAW264...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29900060/transforming-the-prostatic-tumor-microenvironment-with-oncolytic-virotherapy
#13
Matthew J Atherton, Kyle B Stephenson, Fanny Tzelepis, David Bakhshinyan, Jake K Nikota, Hwan Hee Son, Anna Jirovec, Charles Lefebvre, Anna Dvorkin-Gheva, Ali A Ashkar, Yonghong Wan, David F Stojdl, Eric C Belanger, Rodney H Breau, John C Bell, Fred Saad, Sheila K Singh, Jean-Simone Diallo, Brian D Lichty
Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo . An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899553/ubxn3b-positively-regulates-sting-mediated-antiviral-immune-responses
#14
Long Yang, Leilei Wang, Harshada Ketkar, Jinzhu Ma, Guang Yang, Shuang Cui, Tingting Geng, Dana G Mordue, Toyoshi Fujimoto, Gong Cheng, Fuping You, Rongtuan Lin, Erol Fikrig, Penghua Wang
The ubiquitin regulatory X domain-containing proteins (UBXNs) are likely involved in diverse biological processes. Their physiological functions, however, remain largely unknown. Here we present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling. We employ a tamoxifen-inducible Cre-LoxP approach to generate systemic Ubxn3b knockout in adult mice as the Ubxn3b-null mutation is embryonically lethal. Ubxn3b-/- , like Sting-/- mice, are highly susceptible to lethal herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection, which is correlated with deficient immune responses when compared to Ubxn3b+/+ littermates...
June 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29899428/patient-derived-avian-influenza-a-h5n6-virus-is-highly-pathogenic-in-mice-but-can-be-effectively-treated-by-anti-influenza-polyclonal-antibodies
#15
Weiqi Pan, Haojun Xie, Xiaobo Li, Wenda Guan, Peihai Chen, Beiwu Zhang, Mincong Zhang, Ji Dong, Qian Wang, Zhixia Li, Shufen Li, Zifeng Yang, Chufang Li, Nanshan Zhong, Jicheng Huang, Ling Chen
Highly pathogenic avian influenza A (H5N6) virus has been circulating in poultry since 2013 and causes sporadic infections and fatalities in humans. Due to the re-occurrence and continuous evolution of this virus subtype, there is an urgent need to better understand the pathogenicity of the H5N6 virus and to identify effective preventative and therapeutic strategies. We established a mouse model to evaluate the virulence of H5N6 A/Guangzhou/39715/2014 (H5N6/GZ14), which was isolated from an infected patient...
June 13, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29899269/a-simple-and-robust-approach-for-evaluation-of-antivirals-using-a-recombinant-influenza-virus-expressing-gaussia-luciferase
#16
Ping Li, Qinghua Cui, Lin Wang, Xiujuan Zhao, Yingying Zhang, Balaji Manicassamy, Yong Yang, Lijun Rong, Ruikun Du
Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resistance, there is an urgent need to develop novel antivirals. In this study, we characterized a recombinant IAV-carrying Gaussia luciferase (Gluc) gene and determined its potential as a tool for evaluating therapeutics...
June 13, 2018: Viruses
https://www.readbyqxmd.com/read/29899106/regulation-of-herpes-simplex-virus-2-protein-kinase-ul13-by-phosphorylation-and-its-role-in-viral-pathogenesis
#17
Naoto Koyanagi, Akihisa Kato, Kosuke Takeshima, Yuhei Maruzuru, Hiroko Kozuka-Hata, Masaaki Oyama, Jun Arii, Yasushi Kawaguchi
UL13 proteins are serine/threonine protein kinases encoded by herpes simplex virus HSV-1 and HSV-2. Although the downstream effects of the HSV protein kinases, mostly those of HSV-1 UL13, have been reported, there is a lack of information on how these viral protein kinases are regulated in HSV-infected cells. In this study, we used a large-scale phosphoproteomic analysis of HSV-2-infected cells to identify a physiological phosphorylation site in HSV-2 UL13 (i.e., Ser-18), and investigated the significance of phosphorylation of this site in HSV-2-infected cell cultures and mice...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29899102/a-dual-motif-in-the-hemagglutinin-of-h5n1-goose-guangdong-like-hpaiv-is-conserved-from-their-early-evolution-and-increases-both-membrane-fusion-ph-and-virulence
#18
Ute Wessels, El-Sayed M Abdelwhab, Jutta Veits, Donata Hoffmann, Svenja Mamerow, Olga Stech, Jan Hellert, Martin Beer, Thomas C Mettenleiter, Jürgen Stech
Zoonotic highly pathogenic avian influenza viruses (HPAIV) have raised serious public health concerns of a novel pandemic. These strains emerge from low-pathogenic precursors by acquisition of a polybasic hemagglutinin (HA) cleavage site, the prime virulence determinant. However, required co-adaptations of the HA early in HPAIV evolution remained uncertain. To address this question, we generated several HA1/HA2 chimeras and point mutants of an H5N1 clade 2.2.2 HPAIV and an H5N1 low-pathogenic strain. Initial surveys of 3385 HPAIV H5 HA sequences revealed frequencies of 0...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29899096/directed-evolution-of-an-influenza-reporter-virus-to-restore-replication-and-virulence-and-enhance-non-invasive-bioluminescence-imaging-in-mice
#19
Hui Cai, Meisui Liu, Charles J Russell
Reporter viruses provide a powerful tool to study infection, yet incorporating a non-essential gene often results in virus attenuation and genetic instability. Here, we used directed evolution of a luciferase-expressing pandemic H1N1 (pH1N1) 2009 influenza A virus in mice to restore replication kinetics and virulence, increase the bioluminescence signal, and maintain reporter gene expression. An unadapted pH1N1 virus with NanoLuc luciferase inserted into the 5' end of the PA gene segment grew to titers 10-fold less than wild-type in MDCK cells and in DBA/2 mice and was less virulent...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29899095/broadly-reactive-human-monoclonal-antibodies-elicited-following-pandemic-h1n1-influenza-virus-exposure-protect-mice-from-highly-pathogenic-h5n1-challenge
#20
Raffael Nachbagauer, David Shore, Hua Yang, Scott K Johnson, Jon D Gabbard, S Mark Tompkins, Jens Wrammert, Patrick C Wilson, James Stevens, Rafi Ahmed, Florian Krammer, Ali H Ellebedy
Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus...
June 13, 2018: Journal of Virology
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