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https://www.readbyqxmd.com/read/28650722/optimized-dna-vaccine-enhanced-by-adjuvant-il28b-induces-protective-immune-responses-against-herpes-simplex-virus-type-2-in-mice
#1
Yan Zhou, Ziyan Wang, Yongqing Xu, Zeqiang Zhang, Rui Hua, Wei Liu, Chunlai Jiang, Yan Chen, Wenying Yang, Wei Kong
Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...
June 26, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28649380/gitr-ligand-fusion-protein-agonist-enhances-the-tumor-antigen-specific-cd8-t-cell-response-and-leads-to-long-lasting-memory
#2
Nick M Durham, Nick Holoweckyj, Randall S MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H Robbins
BACKGROUND: The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. METHODS: We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28649242/an-approach-for-a-synthetic-ctl-vaccine-design-against-zika-flavivirus-using-class-i-and-class-ii-epitopes-identified-by-computer-modeling
#3
Edecio Cunha-Neto, Daniela S Rosa, Paul E Harris, Tim Olson, Alex Morrow, Serban Ciotlos, Charles V Herst, Reid Martin Rubsamen
The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28647507/differential-replication-of-foot-and-mouth-disease-viruses-in-mice-determine-lethality
#4
Marco Cacciabue, María Soledad García-Núñez, Fernando Delgado, Anabella Currá, Rubén Marrero, Paula Molinari, Elizabeth Rieder, Elisa Carrillo, María Inés Gismondi
Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line...
June 22, 2017: Virology
https://www.readbyqxmd.com/read/28647381/leukotriene-receptor-antagonist-attenuated-airway-inflammation-and-hyperresponsiveness-in-a-double-stranded-rna-induced-asthma-exacerbation-model
#5
Mariko Ujino, Naoya Sugimoto, Yuta Koizumi, Shoki Ro, Yasuhiro Kojima, Kamiyama-Hara Asae, Naomi Yamashita, Ken Ohta, Hiroyuki Nagase
BACKGROUND: Viral infections are the most common triggers of asthma exacerbation, but the key molecules involved in this process have not been fully identified. Although cysteinyl leukotrienes (cysLTs) have been postulated as the key mediators, their precise roles remain largely unclear. To investigate the roles of cysLTs in virus-induced asthma exacerbation, we developed a murine model using a viral double-stranded RNA analog, polyinosinic-polycytidylic acid (poly I:C), and analyzed the effect of leukotriene receptor antagonist (LTRA) administration...
June 21, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28646885/comparison-of-the-protective-efficacy-between-single-and-combination-of-recombinant-adenoviruses-expressing-complete-and-truncated-glycoprotein-and-nucleoprotein-of-the-pathogenic-street-rabies-virus-in-mice
#6
Ha-Hyun Kim, Dong-Kun Yang, Jin-Ju Nah, Jae-Young Song, In-Soo Cho
BACKGROUND: Rabies is an important viral zoonosis that causes acute encephalitis and death in mammals. To date, several recombinant vaccines have been developed based on G protein, which is considered to be the main antigen, and these vaccines are used for rabies control in many countries. Most recombinant viruses expressing RABV G protein retain the G gene from attenuated RABV. Not enough is currently known about the protective effect against RABV of a combination of recombinant adenoviruses expressing the G and N proteins of pathogenic street RABV...
June 24, 2017: Virology Journal
https://www.readbyqxmd.com/read/28646802/dampness-can-promote-the-influenza-a-virus-and-worsen-its-prognosis-by-upregulating-the-tlr7-signaling-pathway
#7
Deng Li, Xu Huachong, Pang Peng, Zheng Ke, Nie Jiao, Wu Xianlin, Yu Bin, Chen Jia, Chen Xiaoyin
Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646616/curcumin-alleviates-macrophage-activation-and-lung-inflammation-induced-by-influenza-virus-infection-through-inhibiting-the-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Yiming Xu, Ling Liu
BACKGROUND: Influenza A viruses (IAV) result in severe public health problems with worldwide each year. Over-response of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality. OBJECTIVE: Curcumin has been reported to have anti-inflammatory ability. However, its molecular mechanism in immune responses remains unclear. METHODS: We detected the pro-inflammatory cytokine secretion and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment...
June 24, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#9
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646236/rapamycin-adjuvant-and-exacerbation-of-severe-influenza-in-an-experimental-mouse-model
#10
Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646206/crispr-cas9-mediated-genome-editing-via-postnatal-administration-of-aav-vector-cures-haemophilia-b-mice
#11
Tsukasa Ohmori, Yasumitsu Nagao, Hiroaki Mizukami, Asuka Sakata, Shin-Ichi Muramatsu, Keiya Ozawa, Shin-Ichi Tominaga, Yutaka Hanazono, Satoshi Nishimura, Osamu Nureki, Yoichi Sakata
Haemophilia B, a congenital haemorrhagic disease caused by mutations in coagulation factor IX gene (F9), is considered an appropriate target for genome editing technology. Here, we describe treatment strategies for haemophilia B mice using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system. Administration of adeno-associated virus (AAV) 8 vector harbouring Staphylococcus aureus Cas9 (SaCas9) and single guide RNA (sgRNA) to wild-type adult mice induced a double-strand break (DSB) at the target site of F9 in hepatocytes, sufficiently developing haemophilia B...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646196/nucleoside-reverse-transcriptase-inhibitors-nrtis-induce-proinflammatory-cytokines-in-the-cns-via-wnt5a-signaling
#12
Ting Wu, Juan Zhang, Mingxing Geng, Shao-Jun Tang, Wenping Zhang, Jianhong Shu
HAART is very effective in suppressing HIV-1 replication in patients. However, patients staying on long-term HAART still develop various HIV-associated neurological disorders, even when the viral load is low. The underlying pathogenic mechanisms are largely unknown. Emerging evidence implicated that persistent neuroinflammation plays an important role in NeuroAIDS. Although residual virus or viral proteins are commonly thought as the causal factors, we are interested in the alternative possibility that HAART critically contributes to the neuroinflammation in the central nervous system (CNS)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#13
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28646038/aging-impairs-alveolar-macrophage-phagocytosis-and-increases-influenza-induced-mortality-in-mice
#14
Christine K Wong, Candice A Smith, Koji Sakamoto, Naftali Kaminski, Jonathan L Koff, Daniel R Goldstein
Influenza viral infections often lead to increased mortality in older people. However, the mechanisms by which aging impacts immunity to influenza lung infection remain unclear. We employed a murine model of influenza infection to identify these mechanisms. With aging, we found reduced numbers of alveolar macrophages, cells essential for lung homeostasis. We also determined that these macrophages are critical for influenza-induced mortality with aging. Furthermore, aging vastly alters the transcriptional profile and specifically downregulates cell cycling pathways in alveolar macrophages...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645311/zika-virus-tropism-and-interactions-in-myelinating-neural-cell-cultures-cns-cells-and-myelin-are-preferentially-affected
#15
Stephanie L Cumberworth, Jennifer A Barrie, Madeleine E Cunningham, Daniely Paulino Gomes de Figueiredo, Verena Schultz, Adrian J Wilder-Smith, Benjamin Brennan, Lindomar J Pena, Rafael Freitas de Oliveira França, Christopher Linington, Susan C Barnett, Hugh J Willison, Alain Kohl, Julia M Edgar
The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV...
June 23, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28645309/herpes-simplex-virus-1-infects-the-olfactory-bulb-shortly-following-ocular-infection-and-exhibits-a-long-term-inflammatory-profile-in-the-form-of-effector-and-hsv-1-specific-t-cells
#16
Chandra M Menendez, Daniel J J Carr
BACKGROUND: Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28645308/neonatal-aav-delivery-of-alpha-synuclein-induces-pathology-in-the-adult-mouse-brain
#17
Marion Delenclos, Ayman H Faroqi, Mei Yue, Aishe Kurti, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W Dickson, John D Fryer, Pamela J McLean
Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases...
June 23, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#18
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28642465/structural-basis-for-biologically-relevant-mechanical-stiffening-of-a-virus-capsid-by-cavity-creating-or-spacefilling-mutations
#19
Pablo Guerra, Alejandro Valbuena, Jordi Querol-Audí, Cristina Silva, Milagros Castellanos, Alicia Rodríguez-Huete, Damià Garriga, Mauricio G Mateu, Nuria Verdaguer
Recent studies reveal that the mechanical properties of virus particles may have been shaped by evolution to facilitate virus survival. Manipulation of the mechanical behavior of virus capsids is leading to a better understanding of viral infection, and to the development of virus-based nanoparticles with improved mechanical properties for nanotechnological applications. In the minute virus of mice (MVM), deleterious mutations around capsid pores involved in infection-related translocation events invariably increased local mechanical stiffness and interfered with pore-associated dynamics...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642154/a-boosting-skin-vaccination-with-dissolving-microneedle-patch-encapsulating-m2e-vaccine-broadens-the-protective-efficacy-of-conventional-influenza-vaccines
#20
Wandi Zhu, Winston Pewin, Chao Wang, Yuan Luo, Gilbert X Gonzalez, Teena Mohan, Mark R Prausnitz, Bao-Zhong Wang
The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulate into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone...
June 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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