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https://www.readbyqxmd.com/read/29666618/reassortant-h5n1-avian-influenza-virus-bearing-pb2-gene-from-a-2009-pandemic-h1n1-exhibits-increased-pathogenicity-in-mice
#1
Xian Lin, Shiman Yu, Kelei Guo, Xin Sun, Haiming Yi, Meilin Jin
Reassortment is a key driving force of the evolution and host adaptation of the influenza virus. A(H1N1)pdm2009 (pdm09), a novel H1N1 influenza viral subtype, caused a pandemic in 2009. The strain was established in pig herds and cocirculated with the highly pathogenic H5N1 avian influenza virus. The coexistence of pdm09 with H5N1 raises concerns that reassortment may cause the development of novel viral strains with unpredictable virulence. Given that the viral polymerase subunit PB2 is a determinant of host range and pathogenicity, and that the substantial amino acid differences in PB2 between pdm09 and H5N1, including positions 590/591 and 271, which are shown to play key roles in enhanced polymerase activity in mammalian host cells, we generated a reassortant virus containing PB2 derived from a pdm09 (A/Liaoning/1/2009, LN/09) to investigate if pdm09-derived PB2 can function in a heterologous avian virus isolate as an adaptive strategy, with H5N1 (A/duck/Hubei/hangmei01/2006, HM/06) as the backbone...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29666403/intact-interleukin-10-receptor-signaling-protects-from-hippocampal-damage-elicited-by-experimental-neurotropic-virus-infection-of-sjl-mice
#2
Ann-Kathrin Uhde, Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Niko Hensel, Peter Claus, Michael Beckstette, René Teich, Stefan Floess, Wolfgang Baumgärtner, Klaus Jung, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis virus (TMEV) infection represents an experimental mouse model to study hippocampal damage induced by neurotropic viruses. IL-10 is a pleiotropic cytokine with profound anti-inflammatory properties, which critically controls immune homeostasis. In order to analyze IL-10R signaling following virus-induced polioencephalitis, SJL mice were intracerebrally infected with TMEV. RNA-based next generation sequencing revealed an up-regulation of Il10, Il10rα and further genes involved in IL-10 downstream signaling, including Jak1, Socs3 and Stat3 in the brain upon infection...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666290/viral-diversity-of-house-mice-in-new-york-city
#3
Simon H Williams, Xiaoyu Che, Joel A Garcia, John D Klena, Bohyun Lee, Dorothy Muller, Werner Ulrich, Robert M Corrigan, Stuart Nichol, Komal Jain, W Ian Lipkin
The microbiome of wild Mus musculus (house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Unbiased high-throughput sequencing of feces revealed 36 viruses from 18 families and 21 genera, including at least 6 novel viruses and 3 novel genera...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29666167/a-flexible-mhc-class-i-multimer-loading-system-for-large-scale-detection-of-antigen-specific-t-cells
#4
Jolien J Luimstra, Malgorzata A Garstka, Marthe C J Roex, Anke Redeker, George M C Janssen, Peter A van Veelen, Ramon Arens, J H Frederik Falkenburg, Jacques Neefjes, Huib Ovaa
Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide-MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29665972/intranasal-delivery-of-influenza-antigen-by-nanoparticles-but-not-nkt-cell-adjuvant-differentially-induces-the-expression-of-b-cell-activation-factors-in-mice-and-swine
#5
Sankar Renu, Santosh Dhakal, Eunsoo Kim, Jonathan Goodman, Yashavanth S Lakshmanappa, Michael J Wannemuehler, Balaji Narasimhan, Prosper N Boyaka, Gourapura J Renukaradhya
Intranasal vaccination of pigs with poly lactic-co-glycolic acid and polyanhydride nanoparticles delivered inactivated influenza virus provides cross-reactive T-cell response, but not antibody response, resulting in incomplete protection and no reduction in nasal virus shedding. Expression of BAFF and Th2 transcription factor GATA-3 were downregulated in lungs of pigs vaccinated with influenza nanovaccine, but in mice it upregulated the expression of BAFF and cytokine TGFβ in cervical lymph nodes. However, the intranasal iNKT cell adjuvant, α-Galctosylceramide upregulates the expression of BAFF in pig lungs...
April 11, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29665376/insect-cell-produced-recombinant-protein-subunit-vaccines-protect-against-zika-virus-infection
#6
Panke Qu, Wei Zhang, Dapeng Li, Chao Zhang, Qingwei Liu, Xueyang Zhang, Xuesong Wang, Wenlong Dai, Yongfen Xu, Qibin Leng, Jin Zhong, Xia Jin, Zhong Huang
Infection with Zika virus (ZIKV) may lead to severe neurologic disorders. It is of significant importance and urgency to develop safe and effective vaccines to prevent ZIKV infection. Here we report the development of ZIKV subunit vaccines based on insect cell-produced recombinant proteins. The N-terminal approximately 80% region (designated as E80) and the domain III (designated as EDIII) of ZIKV envelope (E) protein were efficiently produced as secreted proteins in a Drosophila S2 cell expression system. Both E80 and EDIII could inhibit ZIKV infection in vitro, suggesting that they may have folded properly to display native conformations...
April 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29665374/spectrum-of-activity-testing-for-therapeutics-against-all-four-dengue-virus-serotypes-in-ag129-mouse-models-proof-of-concept-studies-with-the-adenosine-nucleoside-inhibitor-nitd-008
#7
Gregg N Milligan, Mellodee White, Diana Zavala, Richard B Pyles, Vanessa V Sarathy, Alan D T Barrett, Nigel Bourne
Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes...
April 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29662006/hyperinsulinemia-promotes-esophageal-cancer-development-in-a-surgically-induced-duodeno-esophageal-reflux-murine-model
#8
Diletta Arcidiacono, Arben Dedja, Cinzia Giacometti, Matteo Fassan, Daniele Nucci, Simona Francia, Federico Fabris, Alice Zaramella, Emily J Gallagher, Mauro Cassaro, Massimo Rugge, Derek LeRoith, Alfredo Alberti, Stefano Realdon
Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux...
April 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29661824/development-of-dengue-virus-serotype-specific-ns1-capture-assays-for-the-rapid-and-highly-sensitive-identification-of-the-infecting-serotype-in-human-sera
#9
Katharina Röltgen, Natalie Rose, Alessia Ruggieri, Louisa Warryn, Nicole Scherr, Carlos Augusto Pinho-Nascimento, Marco Tamborrini, Thomas Jaenisch, Gerd Pluschke
Dengue fever can be caused by one of four distinct dengue virus (DENV) serotypes that cocirculate in many parts of the world. Point of care serotype-specific nonstructural protein-1 (NS1) capture assays for the rapid serotyping of DENV in human sera would greatly support epidemiological surveillance and potentially also prognosis in individual patients. To ensure both serotype specificity and broad coverage of variants within serotypes, we have applied an innovative approach for the generation and selection of serotype-specific anti-NS1 mAbs...
April 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29661811/murine-models-of-hepatitis-a-virus-infection
#10
Asuka Hirai-Yuki, Jason K Whitmire, Michael Joyce, D Lorne Tyrrell, Stanley M Lemon
Mechanistic analyses of hepatitis A virus (HAV)-induced pathogenesis have long been thwarted by the lack of tractable small animal models that recapitulate disease observed in humans. Several approaches have shown success, including infection of chimeric mice with human liver cells. Other recent studies show that HAV can replicate to high titer in mice lacking expression of the type I interferon (IFN) receptor (IFN-α/β receptor) or mitochondrial antiviral signaling (MAVS) protein. Mice deficient in the IFN receptor show critical features of type A hepatitis in humans when challenged with human HAV, including histological evidence of liver damage, leukocyte infiltration, and the release of liver enzymes into blood...
April 16, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29660337/effect-of-betulinic-acid-and-its-ionic-derivatives-on-m-mulv-replication
#11
Jasmine Phillips, Iesha Phillips, Blessing Enya, Hua Zhao, Takayuki Nitta
Murine leukemia virus (MuLV) is a retrovirus known causing leukemia and neurological disorders in mice, and its viral life cycle and pathogenesis have been investigated extensively over the past decades. As a natural antiviral agent, betulinic acid is a pentacyclic triterpenoid that can be found in the bark of several species of plants (particularly the white birch). One of the hurdles for betulinic acid to release its antiviral potency is its poor water solubility. In this study, we synthesized more water-soluble ionic derivatives of betulinic acid, and examined their activities against Moloney MuLV (M-MuLV)...
April 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29659904/coinfection-with-zika-and-dengue-viruses-results-in-preferential-zika-transmission-by-vector-bite-to-vertebrate-host
#12
Barbara Aparecida Chaves, Alessandra Silva Orfano, Paula Monalisa Nogueira, Nilton Barnabe Rodrigues, Thais Bonifácio Campolina, Rafael Nacif-Pimenta, Ana Clara Araújo Machado Pires, Ademir Bentes Vieira Júnior, Andréia da Costa Paz, Evelyn Beatriz da Costa Vaz, Maria das Graças Vale Barbosa Guerra, Breno Melo Silva, Fabrício Freire de Melo, Douglas Eric Norris, Marcus Vinícius Guimarães de Lacerda, Paulo Filemon Paolucci Pimenta, Nágila Francinete Costa Secundino
Background: Several tropical cities are permissive to Aedes aegypti and DENV endemicity, and have allowed for invasion and circulation of ZIKV in the same areas. People living in endemic regions have been simultaneously infected with two or more arboviruses. Methods: Ae. aegypti mosquitoes from Manaus, capital city of the Amazonas State, were coinfected with circulating strains of DENV and ZIKV. The coinfected vectors were allowed to bite BALB/c mice. Results: Ae...
April 6, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29659579/replication-incompetent-rabies-virus-vector-harboring-glycoprotein-gene-of-lymphocytic-choriomeningitis-virus-lcmv-protects-mice-from-lcmv-challenge
#13
Mutsuyo Takayama-Ito, Chang-Kweng Lim, Yukie Yamaguchi, Guillermo Posadas-Herrera, Hirofumi Kato, Itoe Iizuka, Md Taimur Islam, Kinjiro Morimoto, Masayuki Saijo
BACKGROUND: Lymphocytic choriomeningitis virus (LCMV) causes a variety of diseases, including asymptomatic infections, meningitis, and congenital infections in the fetus of infected mother. The development of a safe and effective vaccine against LCMV is imperative. This study aims to develop a new candidate vaccine against LCMV using a recombinant replication-incompetent rabies virus (RV) vector. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have generated a recombinant deficient RV expressing the LCMV glycoprotein precursor (GPC) (RVΔP-LCMV/GPC) which is lacking the RV-P gene...
April 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29659361/-one-hundred-years-after-the-spanish-flu
#14
Isabel A Lüthy, Viviana Ritacco, Isabel N Kantor
The "Spanish" flu pandemic, which occurred a century ago, is considered the most devastating in human history. An estimated one third of world population fell ill with flu and more than 2.5% of them died. The course of the epidemic had two main waves (1918 and 1919) and showed an unusual W-shaped morbidity/mortality distribution. Death was not a direct outcome of flu itself but rather a consequence of secondary bacterial bronchopneumonia, for which antibiotics had not yet been discovered. Pre-existing pulmonary tuberculosis was also accountable for increased flu death rates during the pandemic...
2018: Medicina
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#15
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29657407/intranasal-administration-of-inactivated-avian-influenza-virus-of-h5n1-subtype-vaccine-induced-systemic-immune-response-in-chicken-and-mice
#16
I N Suartha, G A A Suartini, I W Wirata, N M A R K Dewi, G N N Putra, G A Y Kencana, G N Mahardika
Aim: The need for non-parenteral administration of inactivated avian influenza virus of H5N1 subtype (AIV-H5N1) vaccine is paramount. Here, we provide preliminary data on the immune response of chicken and mice after intranasal administration of AIV-H5N1-inactivated vaccine with ISCOMS, Inmunair (INM), and combined ISCOMS and INM as an adjuvant. Materials and Methods: The AIV isolate of A/Chicken/Denpasar/01/2004 (H5N1) was cultivated in specific pathogen-free chicken eggs and inactivated with formaldehyde...
February 2018: Veterinary World
https://www.readbyqxmd.com/read/29655638/attenuation-of-the-niemann-pick-type-c2-disease-phenotype-by-intracisternal-administration-of-an-aavrh-10-vector-expressing-npc2
#17
Sandra Markmann, Jasmine Reid, Jonathan B Rosenberg, Bishnu P De, Stephen M Kaminsky, Ronald G Crystal, Dolan Sondhi
Niemann-Pick type C2 (NPC2) disease is a rare, neurodegenerative disorder caused by mutations in the NPC2 gene, leading to lysosomal accumulation of unesterified cholesterol and other lipids. It is characterized by hepatosplenomegaly, liver dysfunction and severe neurological manifestations, resulting in early death. There is no effective therapy for NPC2 disease. Here, we evaluated the effectiveness of an adeno-associated virus (AAV), serotype rh.10 gene transfer vector expressing the mouse Npc2 gene (AAVrh...
April 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29655629/intramuscular-vaccination-of-guinea-pigs-with-the-live-attenuated-human-herpes-simplex-vaccine-vc2-stimulates-a-transcriptional-profile-of-vaginal-th17-and-regulatory-tr1-responses
#18
Brent A Stanfield, Paul J F Rider, John Caskey, Fabio Del Piero, Konstantin G Kousoulas
Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig represents the best small animal model of genital HSV-2 disease...
April 11, 2018: Vaccine
https://www.readbyqxmd.com/read/29651984/ifn-%C3%AE-prevents-influenza-virus-spread-from-the-upper-airways-to-the-lungs-and-limits-virus-transmission
#19
Jonas Klinkhammer, Daniel Schnepf, Liang Ye, Marilena Schwaderlapp, Hans Henrik Gad, Rune Hartmann, Dominique Garcin, Tanel Mahlakõiv, Peter Staeheli
Host factors restricting the transmission of respiratory viruses are poorly characterized. We analyzed the contribution of type I and type III interferon (IFN) using a mouse model in which the virus is selectively administered to the upper airways, mimicking a natural respiratory virus infection. Mice lacking functional IFN-λ receptors ( Ifnlr1-/- ) no longer restricted virus dissemination from the upper airways to the lungs. Ifnlr1-/- mice shed significantly more infectious virus particles via the nostrils and transmitted the virus much more efficiently to naïve contacts compared with wild-type mice or mice lacking functional type I IFN receptors...
April 13, 2018: ELife
https://www.readbyqxmd.com/read/29650384/the-effect-of-combined-drugs-therapy-on-the-course-of-clinical-rabies-infection-in-a-murine-model
#20
Marcin Smreczak, Anna Orłowska, Anna Marzec, Paweł Trębas, Anna Kycko, Michał Reichert, Penelope Koraka, Albert D M E Osterhaus, Jan Franciszek Żmudziński
Rabies is a fatal disease of all mammals causing almost 60,000 human deaths every year. To date, there is no effective treatment of clinical rabies once the symptoms appear. Here, we describe the promising effect of combination therapy composed of molecules that target replication of the rabies virus (RV) at different stages of life cycle and molecules that inhibit some pathways of the innate host immune response accompanied by a blood-brain barrier opener on the outcome of RV infection. The study reports statistically significant extension of survival of mice treated with the drug cocktail containing T-705, ribavirin, interferon α/β, caspase-1 inhibitor, TNF-α inhibitor, MAPKs inhibitor and HRIG compared to the survival of mice in the virus control group (p = 0...
April 9, 2018: Vaccine
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