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https://www.readbyqxmd.com/read/27911409/measuring-progressive-neurological-disability-in-a-mouse-model-of-multiple-sclerosis
#1
Francesca Gilli, Darlene B Royce, Andrew R Pachner
After intracerebral infection with the Theiler's Murine Encephalomyelitis Virus (TMEV), susceptible SJL mice develop a chronic-progressive demyelinating disease, with clinical features similar to the progressive forms of multiple sclerosis (MS). The mice show progressive disability with loss of motor and sensory functions, which can be assessed with multiple apparatuses and protocols. Among them, the Rotarod performance test is a very common behavioral test, its advantage being that it provides objective measurements, but it is often used assuming that it is straightforward and simple...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910950/human-antibody-3e1-targets-the-ha-stem-region-of-h1n1-and-h5n6-influenza-a-viruses
#2
Wenshuai Wang, Xiaoyu Sun, Yanbing Li, Jinpeng Su, Zhiyang Ling, Tianlong Zhang, Fang Wang, Hong Zhang, Hualan Chen, Jianping Ding, Bing Sun
As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27909702/complement-inhibition-enables-tumor-delivery-of-lcmv-glycoprotein-pseudotyped-viruses-in-the-presence-of-antiviral-antibodies
#3
Laura Evgin, Carolina S Ilkow, Marie-Claude Bourgeois-Daigneault, Christiano Tanese de Souza, Lawton Stubbert, Michael S Huh, Victoria A Jennings, Monique Marguerie, Sergio A Acuna, Brian A Keller, Charles Lefebvre, Theresa Falls, Fabrice Le Boeuf, Rebecca A Auer, John D Lambris, J Andrea McCart, David F Stojdl, John C Bell
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#4
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27908830/protective-efficacy-of-fc-targeting-conserved-influenza-virus-m2e-antigen-expressed-by-lactobacillus-plantarum
#5
Wen-Tao Yang, Gui-Lian Yang, Qian Wang, Hai-Bin Huang, Yan-Long Jiang, Chun-Wei Shi, Jian-Zhong Wang, Ke-Yan Huang, Yu-Bei Jin, Chun-Feng Wang
The influenza A (H1N1) virus is a highly contagious acute respiratory disease affecting pigs and humans. This disease causes severe economic loss in many countries, and developing mucosal vaccines is an efficient strategy to control the influenza virus. The neonatal Fc receptor (FcRn) plays an important role in transferring IgG across polarized epithelial cells. In the present study, an oral vaccine was developed using Lactobacillus plantarum to deliver the internal influenza viral protein M2e fused to an IgG Fc fragment...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908639/animal-models-of-respiratory-syncytial-virus-infection
#6
Geraldine Taylor
Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success...
November 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27905537/unique-nonstructural-proteins-of-pneumonia-virus-of-mice-pvm-promote-degradation-of-interferon-ifn-pathway-components-and-ifn-stimulated-gene-proteins
#7
Jayeeta Dhar, Sailen Barik
Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903977/dioscin-augments-hsv-tk-mediated-suicide-gene-therapy-for-melanoma-by-promoting-connexin-based-intercellular-communication
#8
Jianyong Xiao, Guangxian Zhang, Bin Li, Yingya Wu, Xijuan Liu, Yuhui Tan, Biaoyan Du
Suicide gene therapy is a promising strategy against melanoma. However, the low efficiency of the gene transfer technique can limit its application. Our preliminary data showed that dioscin, a glucoside saponin, could upregulate the expression of connexins Cx26 and Cx43, major components of gap junctions, in melanoma cells. We hypothesized that dioscin may increase the bystander effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) through increasing the formation of gap junctions. Further analysis showed that dioscin indeed could increase the gap junctional intercellular communication in B16 melanoma cells, resulting in more efficient GCV-induced bystander killing in B16tk cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903802/a-protective-role-for-il-1-signaling-during-mouse-adenovirus-type-1-induced-encephalitis
#9
Luiza A Castro-Jorge, Carla Pretto, Asa Smith, Oded Foreman, Kelly E Carnahan, Katherine R Spindler
: IL-1β, an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor, Il1r1(-/-) Il1r1(-/-) mice had lower survival, higher disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokines and chemokines than control C57BL/6 mice. We also examined infections of mice defective in IL-1β production (Pycard(-/-)mice) and mice defective in trafficking of TLRs to the endosome (Unc93b1(-/-) mice)...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903277/sequence-diversity-of-dengue-virus-type-2-in-brain-and-thymus-of-infected-interferon-receptor-ko-mice-implications-for-dengue-virulence
#10
Priya Dhole, Emi E Nakayama, Akatsuki Saito, Kriengsak Limkittikul, Supranee Phanthanawiboon, Tatsuo Shioda, Takeshi Kurosu
BACKGROUND: We previously reported that a clinical isolate of dengue virus (DENV) is capable of causing acute-phase systemic infection in mice harboring knockouts of the genes encoding type-I and -II interferon IFN receptors (IFN-α/β/γR KO mice); in contrast, other virulent DENV isolates exhibited slow disease progression in this mice, yielding lethal infection around 20 days post-infection (p.i.). In the present study, we sought to clarify the dynamics of slow disease progression by examining disease progression of a type-2 DENV clinical isolate (DV2P04/08) in mice...
November 30, 2016: Virology Journal
https://www.readbyqxmd.com/read/27903271/differential-humoral-and-cellular-immunity-induced-by-vaccination-using-plasmid-dna-and-protein-recombinant-expressing-the-ns3-protein-of-dengue-virus-type-3
#11
M L Hurtado-Melgoza, A Ramos-Ligonio, L M Álvarez-Rodríguez, T Meza-Menchaca, A López-Monteon
BACKGROUND: The dengue non-structural 3 (NS3) is a multifunctional protein, containing a serine-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus...
December 1, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27902933/the-fda-approved-drug-sofosbuvir-inhibits-zika-virus-infection
#12
Kristen M Bullard-Feibelman, Jennifer Govero, Zhe Zhu, Vanessa Salazar, Milena Veselinovic, Michael S Diamond, Brian J Geiss
The rapidly expanding Zika virus (ZIKV) epidemic has affected thousands of individuals with severe cases causing Guillain-Barré syndrome, congenital malformations, and microcephaly. Currently, there is no available vaccine or therapy to prevent or treat ZIKV infection. We evaluated whether sofosbuvir, an FDA-approved nucleotide polymerase inhibitor for the distantly related hepatitis C virus, could have antiviral activity against ZIKV infection. Cell culture studies established that sofosbuvir efficiently inhibits replication and infection of several ZIKV strains in multiple human tumor cell lines and isolated human fetal-derived neuronal stem cells...
November 27, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902899/endemic-variation-of-h9n2-avian-influenza-virus-in-china
#13
Yu-Fu Liu, Han-Zhang Lai, Lin Li, Yu-Peng Liu, Wen-Yan Zhang, Ren Gao, Wen-Ke Huang, Qin-Fang Luo, Yan Gao, Qiong Luo, Xiao-Yu Xie, Jia-Hua Xu, Rui-Ai Chen
Forty-two H9N2 subtype AIV strains were isolated from vaccinated commercial chickens in China from 2012 to 2015. Their HA genes had nucleotide sequence homology from 86.7% to 99.7%, and similarity to the classic vaccine strain was 88.6%-92.6%. A comparison was carried out with published HA genes (410 H9 strains) and whole genomes (306 strains) isolated in China during 2012-2015. Interestingly, 99.1% (448/452) of Chinese H9N2 AIV belonged to lineage h9.4.2, and 98.5% (445/452) of the viruses belonged to h9.4...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902762/presenting-influenza-a-m2e-antigen-on-recombinant-spores-of-bacillus-subtilis
#14
Tomasz Łęga, Paulina Weiher, Michał Obuchowski, Dawid Nidzworski
Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses...
2016: PloS One
https://www.readbyqxmd.com/read/27902386/establishment-of-memory-cd8-t-cells-with-live-attenuated-influenza-virus-laiv-across-different-vaccination-doses
#15
Zhongfang Wang, Lukasz Kedzierska, Simone Nuessing, Brendon Chua, Sergio M Quiñones-Parra, Victor C Huber, David Jackson, Paul G Thomas, Katherine Kedzierska
FluMist has been used in children and adults for more than ten years. As pre-existing CD8+ T-cell memory pools can provide heterologous immunity against distinct influenza viruses, it is important to understand influenza-specific CD8+ T-cell responses elicited by different LAIV regimens. In this study, we immunized mice intranasally (i.n.) with two different doses of live-attenuated PR8 virus (PR8 ts, H1N1), low and high, and then assessed protective efficacy by challenging animals with heterosubtypic X31-H3N2 virus at 6 weeks post-vaccination...
November 2, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902385/motor-coordination-and-balance-measurements-reveal-differential-pathogenicity-of-currently-spreading-ev71-strains-in-human-scarb2-transgenic-mice
#16
Mei-Feng Chen, Shin-Ru Shih
Enterovirus 71 (EV71) has caused large-scale epidemics with neurological complications in Asia Pacific region. The C4a and B5 strains are the two major genotypes circulalted in many coutries recently. This study provides a new protocol, a motor coordination task, to assess the differential pathogenicity of C4a and B5 strains in human SCARB2 transgenic mice. We found that the pathogenicity of C4a viruses was more severe than that of B5 viruses. Moreover, we discovered that an increased level of monocyte chemoattractant protein-1 is positively correlated with severely deficient motor function...
October 20, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902351/protective-role-of-cx3cr1-signaling-in-resident-cells-of-the-central-nervous-system-during-experimental-herpes-simplex-virus-encephalitis
#17
Rafik Menasria, Coraline Canivet, Jocelyne Piret, Jean Gosselin, Guy Boivin
CX3CR1 is an important chemokine receptor expressed on the surface of microglia and blood leukocytes including monocytes. Signaling through this receptor influences the immune activity of microglia and monocytes trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CX3CR1 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CX3CR1 expressed in resident cells of the CNS or peripheral monocytes in protection against HSE remains unclear...
November 30, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902338/recombinant-rabies-virus-expressing-il-21-enhances-immunogenicity-through-activation-of-t-follicular-helper-cells-and-germinal-center-b-cells
#18
Yajing Zhang, Ming Zhou, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao
Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signaling could affect specific antibody induction after rabies vaccination. Here, to further investigate the overexpression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated as LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that mice immunized with LBNSE-IL21 could substantially increase the number of T follicular helper (Tfh) cells and germinal center (GC) B cells but did not enhance dendritic cell (DC) activation...
October 25, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901098/tumor-specific-delivery-of-biologics-by-a-novel-t-cell-line-hozot
#19
Teppei Onishi, Hiroshi Tazawa, Yuuri Hashimoto, Makoto Takeuchi, Takeshi Otani, Shuji Nakamura, Fuminori Sakurai, Hiroyuki Mizuguchi, Hiroyuki Kishimoto, Yuzo Umeda, Yasuhiro Shirakawa, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
"Cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900002/therapeutic-targeting-of-liver-cancer-with-a-recombinant-dna-vaccine-containing-the-hemagglutinin-neuraminidase-gene-of-newcastle-disease-virus-via-apoptotic-dependent-pathways
#20
Li-Gang Chen, Yuan-Sheng Liu, Tang-Hui Zheng, Xu Chen, Ping Li, Chuan-Xing Xiao, Jian-Lin Ren
A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer...
November 2016: Oncology Letters
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