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https://www.readbyqxmd.com/read/28820694/differential-neurovirulence-of-african-and-asian-genotype-zika-virus-isolates-in-outbred-immunocompetent-mice
#1
Nisha K Duggal, Jana M Ritter, Erin M McDonald, Hannah Romo, Farshad Guirakhoo, Brent S Davis, Gwong-Jen J Chang, Aaron C Brault
Although first isolated almost 70 years ago, Zika virus (ZIKV; Flavivirus, Flaviviridae) has only recently been associated with significant outbreaks of disease in humans. Several severe ZIKV disease manifestations have also been recently documented, including fetal malformations, such as microcephaly, and Guillain-Barré syndrome in adults. Although principally transmitted by mosquitoes, sexual transmission of ZIKV has been documented. Recent publications of several interferon receptor knockout mouse models have demonstrated ZIKV-induced disease...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28819413/the-role-of-%C3%AE-catenin-in-the-initiation-and-metastasis-of-ta2-mice-spontaneous-breast-cancer
#2
Dan Zhang, Fei Fei, Shuyuan Li, Yongjie Zhao, Zhengduo Yang, Jie Qu, Xipeng Zhang, Yu Yin, Shiwu Zhang
Purpose: Tientsin Albino 2 (TA2) mice have a high incidence of spontaneous breast cancer. Tumor initiation is related to mouse mammary tumor virus (MMTV) infection. MMTV is hormonally regulated and may promote tumor formation via Wnt/β-catenin signaling pathway. This study attempts to clarify the relationship between β-catenin expression and the initiation and metastasis of spontaneous breast cancer in TA2 mice. Materials and Methods: Pathological samples illustrating the development of spontaneous breast cancer in TA2 mice were collected and the presence of virus particles was verified in the cancer tissue by electron microscope...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819261/modified-vaccinia-virus-ankara-preferentially-targets-antigen-presenting-cells-in-vitro-ex-vivo-and-in-vivo
#3
Arwen F Altenburg, Carolien E van de Sandt, Bobby W S Li, Ronan J MacLoughlin, Ron A M Fouchier, Geert van Amerongen, Asisa Volz, Rudi W Hendriks, Rik L de Swart, Gerd Sutter, Guus F Rimmelzwaan, Rory D de Vries
Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819143/immunomodulatory-and-antioxidant-effects-of-total-flavonoids-of-spatholobus-suberectus-dunn-on-pcv2-infected-mice
#4
Yuan-Fang Fu, Li-He Jiang, Wei-Dan Zhao, Meng Xi-Nan, Shi-Qi Huang, Jian Yang, Ting-Jun Hu, Hai-Lan Chen
Oxidative stress plays an important role in the pathogenesis of virus infection and antioxidants are becoming promising candidates as therapeutic agents. This study is designed to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on oxidative stress in mice induced by porcine circovirus type 2 (PCV2) infection. The PCV2 infection leads to significant decrease in thymus and spleen indices, elevation of xanthine oxidase (XOD) and myeloperoxidase (MPO) activities, reduction in GSH level and GSH to GSSG ratio and decline of superoxide dismutase (SOD) activity, indicating the formation of immunosuppression and oxidative stress...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818835/src-dependent-phosphorylation-of-%C3%AE-opioid-receptor-at-tyr-336-modulates-opiate-withdrawal
#5
Lei Zhang, Cherkaouia Kibaly, Yu-Jun Wang, Chi Xu, Kyu Young Song, Patrick W McGarrah, Horace H Loh, Jing-Gen Liu, Ping-Yee Law
Opiate withdrawal/negative reinforcement has been implicated as one of the mechanisms for the progression from impulsive to compulsive drug use. Increase in the intracellular cAMP level and protein kinase A (PKA) activities within the neurocircuitry of addiction has been a leading hypothesis for opiate addiction. This increase requires the phosphorylation of μ-opioid receptor (MOR) at Tyr(336) by Src after prolonged opiate treatment in vitro Here, we report that the Src-mediated MOR phosphorylation at Tyr(336) is a prerequisite for opiate withdrawal in mice...
August 17, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28818572/ribavirin-inhibits-zika-virus-zikv-replication-in-vitro-and-suppresses-viremia-in-zikv-infected-stat1-deficient-mice
#6
Naganori Kamiyama, Ryusuke Soma, Shinya Hidano, Kei Watanabe, Hiroshi Umekita, Chiaki Fukuda, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki, Akira Sonoda, Nozomi Sachi, Lucky Ronald Runtuwene, Yumako Miura, Etsuro Matsubara, Shigeru Tajima, Tomohiko Takasaki, Yuki Eshita, Takashi Kobayashi
Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication...
August 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28818566/a-synthetic-human-cytomegalovirus-pp65-ie1-fusion-antigen-efficiently-induces-and-expands-virus-specific-t-cells
#7
Ellen K Link, Christine Brandmüller, Yasemin Suezer, Stefanie Ameres, Asisa Volz, Andreas Moosmann, Gerd Sutter, Michael H Lehmann
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#8
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28817198/valuable-antibody-detection-method-for-classifying-hepatitis-e-virus-genotypes
#9
Chenyan Zhao, Yansheng Geng, Weijing Huang, Hongxia Ma, Youchun Wang
Nucleotide-based methods are conventionally used to classify the hepatitis E virus (HEV) genotypes. A serological enzyme immunoassay (EIA) using open reading frame 3 (ORF3) C-terminal peptides was developed to conveniently and accurately classify and evaluate the genotypes of HEV. The sera of mice immunized with HEV genotype 1, 3 and 4 reacted highly specifically to the peptides of the corresponding genotypes. Most (84.2%) clinical sera infected with HEV genotype 4 were positive for anti-HEV antibodies when tested with the ORF3 peptides of genotype 4, but were negative for genotypes 1 and 3...
August 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28816082/zeaxanthin-dipalmitate-alleviates-hepatic-injury-induced-by-superimposed-chronic-hepatitis-b-and-non-alcoholic-steatohepatitis-in-non-obese-mice
#10
Jing-Jing Li, Hao Gao, Yi Lv, Mian-Huan Li, Chao-Ran Ren, Kwok-Fai So, Jia Xiao
A hepatitis B virus (HBV) transgenic mice model was used to establish the fatty liver superimposed model by feeding the methionine choline-deficient (MCD) diet for 8 weeks, with or without the gavage of 2 mg/kg zeaxanthin dipalmitate (ZD) three times per week. Both wild-type and HBV transgenic mice, with MCD diet, gained typical non-obese non-alcoholic steatohepatitis (NASH) and HBV symptoms. Coadministration with ZD exhibited evident therapeutic effects through alleviating those pathological events. Moreover, long-term vehicle-ZD treatment was found to be safe...
September 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28815644/role-of-%C3%AE-%C3%AE-t-cells-in-exacerbated-airway-inflammation-during-reinfection-of-neonatally-primed-mice-in-adulthood
#11
Jianqi Wu, Lei Xu, Xu Han, Haiyan Hu, Feifei Qi, Song Bai, Ruonan Chai, Yuee Teng, Beixing Liu
Age at primary infection with respiratory syncytial virus (RSV) is a crucial factor in determining the outcome of reinfection. However, how neonatal RSV infection affects the immune system and renders the host more susceptible to reinfection in later life is poorly understood. In the present study, by using BALB/c mice that were first infected with RSV as neonates, the role of γδ T cells in the development of airway inflammation during reinfection in adulthood was investigated. We found that neonatal RSV infection resulted in an aggravated infiltration of mononuclear cells in bronchoalveolar lavage (BAL) fluids, in parallel with a significant increase in the levels of type 2 cytokines in lungs on day 4 after reinfection...
August 16, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28815049/multi-target-chimaeric-vlp-as-a-therapeutic-vaccine-in-a-model-of-colorectal-cancer
#12
Braeden Donaldson, Farah Al-Barwani, Simon J Pelham, Katie Young, Vernon K Ward, Sarah L Young
BACKGROUND: Colorectal cancer is responsible for almost 700,000 deaths annually worldwide. Therapeutic vaccination is a promising alternative to conventional treatment for colorectal cancer, using vaccines to induce targeted immune responses against tumour-associated antigens. In this study, we have developed chimaeric virus-like particles (VLP), a form of non-infectious non-replicative subunit vaccine consisting of rabbit haemorrhagic disease virus (RHDV) VP60 capsid proteins containing recombinantly inserted epitopes from murine topoisomerase IIα and survivin...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814523/screening-of-fda-approved-drugs-for-inhibitors-against-japanese-encephalitis-virus-infection
#13
Shaobo Wang, Yang Liu, Jiao Guo, Peilin Wang, Leike Zhang, Gengfu Xiao, Wei Wang
Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. There is no approved drug available for JEV-specific treatment, and the vaccines are not effective against all clinical JEV isolates. Herein, a high-throughput screening was performed against JEV from an FDA-approved drug library. Five hit drugs were identified that inhibited JEV infection with a selective index > 10. Antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814513/escape-of-tick-borne-flavivirus-from-2-c-methylated-nucleoside-antivirals-is-mediated-by-a-single-conservative-mutation-in-ns5-that-has-a-dramatic-effect-on-viral-fitness
#14
Ludek Eyer, Hirofumi Kondo, Darina Zouharova, Minato Hirano, James J Valdés, Memi Muto, Tomas Kastl, Shintaro Kobayashi, Jan Haviernik, Manabu Igarashi, Hiroaki Kariwa, Marketa Vaculovicova, Jiri Cerny, Rene Kizek, Andrea Kröger, Stefan Lienenklaus, Milan Dejmek, Radim Nencka, Martin Palus, Jiri Salat, Erik De Clercq, Kentaro Yoshii, Daniel Ruzek
Tick-borne encephalitis virus (TBEV) causes a severe and potentially fatal neuroinfection in humans. Despite its high medical relevance, no specific antiviral therapy is currently available. Here we demonstrate that treatment with a nucleoside analog, 7-deaza-2' -C-methyladenosine (7-deaza-2' -CMA), substantially improved disease outcome, increased survival, and reduced signs of neuroinfection and viral titers in the brains of mice infected with a lethal dose of TBEV. To investigate the mechanism of action of 7-deaza-2' -CMA, two drug-resistant TBEV clones were generated and characterized...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814512/zoonotic-risk-pathogenesis-and-transmission-of-avian-origin-h3n2-canine-influenza-virus
#15
Hailiang Sun, Sherry Blackmon, Guohua Yang, Kaitlyn Waters, Tao Li, Ratanaporn Tangwangvivat, Yifei Xu, Daniel Shyu, Feng Wen, Jim Cooley, Lucy Senter, Xiaoxu Lin, Richard Jarman, Larry Hanson, Richard Webby, Xiu-Feng Wan
Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus H3N2 (CIV-H3N2) and equine-origin CIV-H3N8, are enzootic in the canine population. Dogs have demonstrated seroconversion to diverse IAVs and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antisera we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting there may be minimal herd immunity in humans...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813660/neutralizing-antibody-responses-to-viral-infections-are-linked-to-the-non-classical-mhc-class-ii-gene-h2-ob
#16
Lisa K Denzin, Aly A Khan, Francesca Virdis, Jessica Wilks, Melissa Kane, Helen A Beilinson, Stanislav Dikiy, Laure K Case, Derry Roopenian, Michele Witkowski, Alexander V Chervonsky, Tatyana V Golovkina
Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28811681/osteopontin-impacts-west-nile-virus-pathogenesis-and-resistance-by-regulating-inflammasome-components-and-cell-death-in-the-central-nervous-system-at-early-time-points
#17
Nikki Bortell, Claudia Flynn, Bruno Conti, Howard S Fox, Maria Cecilia G Marcondes
Osteopontin (OPN) is a molecule that is common in central nervous system (CNS) pathologies, which participates in the activation, migration, and survival of inflammatory cells. However, the mechanisms by which OPN modulates inflammatory pathways are not clear. To understand the role of OPN in CNS viral infections, we used a lethal mouse model of West Nile virus (WNV), characterized by the injection of high doses of the Eg101 strain of WNV, causing the increase of OPN levels in the brain since early time points...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28811492/interferon-alpha-treatment-rapidly-clears-hepatitis-e-virus-infection-in-humanized-mice
#18
Martijn D B van de Garde, Suzan D Pas, Gertine W van Oord, Lucio Gama, Youkyung Choi, Robert A de Man, Andre Boonstra, Thomas Vanwolleghem
Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811473/plant-made-polio-type-3-stabilized-vlps-a-candidate-synthetic-polio-vaccine
#19
Johanna Marsian, Helen Fox, Mohammad W Bahar, Abhay Kotecha, Elizabeth E Fry, David I Stuart, Andrew J Macadam, David J Rowlands, George P Lomonossoff
Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28811340/type-iii-interferon-mediated-signaling-is-critical-for-controlling-live-attenuated-yellow-fever-virus-infection-in-vivo
#20
Florian Douam, Yentli E Soto Albrecht, Gabriela Hrebikova, Evita Sadimin, Christian Davidson, Sergei V Kotenko, Alexander Ploss
Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection...
August 15, 2017: MBio
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