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https://www.readbyqxmd.com/read/28717654/fusion-to-flaviviral-leader-peptide-targets-hiv-1-reverse-transcriptase-for-secretion-and-reduces-its-enzymatic-activity-and-ability-to-induce-oxidative-stress-but-has-no-major-effects-on-its-immunogenic-performance-in-dna-immunized-mice
#1
Anastasia Latanova, Stefan Petkov, Yulia Kuzmenko, Athina Kilpeläinen, Alexander Ivanov, Olga Smirnova, Olga Krotova, Sergey Korolev, Jorma Hinkula, Vadim Karpov, Maria Isaguliants, Elizaveta Starodubova
Reverse transcriptase (RT) is a key enzyme in viral replication and susceptibility to ART and a crucial target of immunotherapy against drug-resistant HIV-1. RT induces oxidative stress which undermines the attempts to make it immunogenic. We hypothesized that artificial secretion may reduce the stress and make RT more immunogenic. Inactivated multidrug-resistant RT (RT1.14opt-in) was N-terminally fused to the signal providing secretion of NS1 protein of TBEV (Ld) generating optimized inactivated Ld-carrying enzyme RT1...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28717359/the-c-terminal-effector-domain-of-non-structural-protein-1-of-influenza-a-virus-blocks-ifn-%C3%AE-production-by-targeting-tnf-receptor-associated-factor-3
#2
Wei Qian, Xiaoqin Wei, Kelei Guo, Yongtao Li, Xian Lin, Zhong Zou, Hongbo Zhou, Meilin Jin
Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28716913/antibody-based-assay-discriminates-zika-virus-infection-from-other-flaviviruses
#3
Angel Balmaseda, Karin Stettler, Raquel Medialdea-Carrera, Damaris Collado, Xia Jin, José Victor Zambrana, Stefano Jaconi, Elisabetta Cameroni, Saira Saborio, Francesca Rovida, Elena Percivalle, Samreen Ijaz, Steve Dicks, Ines Ushiro-Lumb, Luisa Barzon, Patricia Siqueira, David W G Brown, Fausto Baldanti, Richard Tedder, Maria Zambon, A M Bispo de Filippis, Eva Harris, Davide Corti
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716893/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-there-is-only-one-true-winner
#4
Scott B Halstead
The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28712817/clinical-features-and-dynamic-ordinary-laboratory-tests-differentiating-dengue-fever-from-other-febrile-illnesses-in-children
#5
Chih-Ho Chen, Yi-Chuan Huang, Kuang-Che Kuo, Chung-Chen Li
BACKGROUND: Dengue fever is not easily to be diagnosed before presentation of the classic symptoms. The study aimed to investigate the clinical features and dynamic laboratory tests in pediatric patients to facilitate dengue diagnosis. METHODS: This retrospective study examined the medical records of all pediatric patients who were clinically suspected to have dengue from June to December 2014. Laboratory-positive dengue cases were confirmed by detecting non-structural protein NS1, reverse transcription-polymerase chain reaction of dengue virus, and dengue-specific IgM seroconversion...
June 30, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28712153/proteomic%C3%A2-analysis-reveals-the-enhancement-of-human-serum-apolipoprotein-a-1-apo-a-1-in%C3%A2-individuals%C3%A2-infected-with-multiple-dengue-virus-serotypes
#6
Manchala Nageswar Reddy, Ranjeet Dungdung, Rajendra Pilankatta
OBJECTIVES: Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. METHODS: Dengue virus NS1 positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins...
July 16, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28708997/vaccine-mediated-protection-against-zika-virus-induced-congenital-disease
#7
Justin M Richner, Brett W Jagger, Chao Shan, Camila R Fontes, Kimberly A Dowd, Bin Cao, Sunny Himansu, Elizabeth A Caine, Bruno T D Nunes, Daniele B A Medeiros, Antonio E Muruato, Bryant M Foreman, Huanle Luo, Tian Wang, Alan D Barrett, Scott C Weaver, Pedro F C Vasconcelos, Shannan L Rossi, Giuseppe Ciaramella, Indira U Mysorekar, Theodore C Pierson, Pei-Yong Shi, Michael S Diamond
The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28706387/comparison-of-nonstructural-protein-1-antigen-detection-by-rapid-and-enzyme-linked-immunosorbent-assay-test-and-its-correlation-with-polymerase-chain-reaction-for-early-diagnosis-of-dengue
#8
Seema Gaikwad, Sandhya S Sawant, Jayanthi S Shastri
INTRODUCTION: Early diagnosis of dengue is important for appropriate clinical management and vector control. Different serological tests based on the principle of immunochromatography and enzyme-linked immunosorbent assay (ELISA) are commonly used for detection of antigen and antibodies of dengue virus. The performance of these tests depends on the sensitivity and specificity. Hence, the study was undertaken to compare nonstructural protein-1 (NS1) antigen detection by rapid and ELISA with real-time polymerase chain reaction (RT-PCR) for diagnosis of dengue...
July 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28698274/noroviruses-co-opt-the-function-of-host-proteins-vapa-and-vapb-for-replication-via-a-phenylalanine-phenylalanine-acidic-tract-motif-mimic-in-nonstructural-viral-protein-ns1-2
#9
Broc T McCune, Wei Tang, Jia Lu, James B Eaglesham, Lucy Thorne, Anne E Mayer, Emily Condiff, Timothy J Nice, Ian Goodfellow, Andrzej M Krezel, Herbert W Virgin
The Norovirus genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28696227/translational-regulation-of-viral-secretory-proteins-by-the-5-coding-regions-and-a-viral-rna-binding-protein
#10
Johan Nordholm, Jeanne Petitou, Henrik Östbye, Diogo V da Silva, Dan Dou, Hao Wang, Robert Daniels
A primary function of 5' regions in many secretory protein mRNAs is to encode an endoplasmic reticulum (ER) targeting sequence. In this study, we show how the regions coding for the ER-targeting sequences of the influenza glycoproteins NA and HA also function as translational regulatory elements that are controlled by the viral RNA-binding protein (RBP) NS1. The translational increase depends on the nucleotide composition and 5' positioning of the ER-targeting sequence coding regions and is facilitated by the RNA-binding domain of NS1, which can associate with ER membranes...
July 10, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28692342/targeting-the-%C3%AE-4-%C3%AE-5-interface-of-ras-results-in-multiple-levels-of-inhibition
#11
Russell Spencer-Smith, Lie Li, Sheela Prasad, Akiko Koide, Shohei Koide, John P O'Bryan
Generation of RAS-targeted therapeutics has long been considered a "holy grail" in cancer research. However, a lack of binding pockets on the surface of RAS and its picomolar affinity for guanine nucleotides have made isolation of inhibitors particularly challenging. We recently described a monobody, termed NS1, that blocks RAS signaling and oncogenic transformation. NS1 binds to the α4-β6-α5 interface of H-RAS and K-RAS thus preventing RAS dimerization and nanoclustering, which in turn prevents RAS-stimulated dimerization and activation of RAF...
July 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28690377/dengue-symptoms-significance-in-anti-dengue-drug-development-road-less-travelled
#12
Anubrata Paul, Arpana Vibhuti
Dengue outbreak has affected rural areas of Delhi-NCR, Haryana widely but it lacks in surveillance. High cases of dengue symptoms were reported in these regions whereas dengue symptoms have been a neglected issue in the anti-dengue drug development. Therefore, this study aims to analyze the status of the dengue infection, a rural issue of Delhi-NCR, Haryana and to identify the significance of dengue symptoms in anti-dengue drug development. The study was conducted when there is high chance of dengue infection i...
2017: Bioinformation
https://www.readbyqxmd.com/read/28683141/isolation-of-serotype-specific-antibodies-against-dengue-virus-non-structural-protein-1-using-phage-display-and-application-in-a-multiplexed-serotyping-assay
#13
Kebaneilwe Lebani, Martina L Jones, Daniel Watterson, Andrea Ranzoni, Renee J Traves, Paul R Young, Stephen M Mahler
The multidimensional nature of dengue virus (DENV) infections, which can be caused by four distinct serotypes of the virus, complicates the sensitivity of assays designed for the diagnosis of infection. Different viral markers can be optimally detected at different stages of infection. Of particular clinical importance is the early identification of infection, which is pivotal for disease management and the development of blood screening assays. Non-structural protein 1 (NS1) is an early surrogate marker of infection and its detection in serum coincides with detectable viraemia...
2017: PloS One
https://www.readbyqxmd.com/read/28681825/co-circulation-of-all-four-dengue-virus-serotypes-first-report-from-odisha
#14
Baijayantimala Mishra, Jyotirmayee Turuk, Subhra Jyoti Sahu, Atul Khajuria, Subrat Kumar, Anupam Dey, Ashok Kumar Praharaj
The present report describes the detection of co-circulation of all the four dengue serotypes along with rarely detected dengue viruses (DENVs)-4 for the first time in Odisha. One hundred and forty-eight blood samples were tested for dengue NS1 antigen ELISA and IgM antibody (Ab), and twenty early samples were subjected for type-specific multiplex reverse transcription-polymerase chain reaction (RT-PCR). Twenty-three samples found positive for dengue NS1 and/or IgM Ab; five were positive by RT-PCR. DENV-4 was detected in one sample, DENV-2 in two and 2 were co-infected with DENV-1 and 3...
April 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28681816/clinical-and-laboratory-profile-of-dengue-viral-infections-in-and-around-mangalore-india
#15
Tina Damodar, Meena Dias, Reeta Mani, K A Shilpa, Ashwini Manoor Anand, V Ravi, Jutang Tiewsoh
BACKGROUND: Dengue (DEN) is being recognised as the world's major emerging tropical disease. Clinically, DEN may resemble other infections such as malaria, leptospirosis, and typhoid, and thus, laboratory investigations are required for definitive diagnosis. Secondary DEN infection, caused most often by dengue virus (DENV) serotypes 2 and 3, is known to present with severe disease manifestations. This study was undertaken to examine the clinical and laboratory profile of DEN viral infections and to determine the circulating serotypes in and around Mangalore, India...
April 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28665409/structural-basis-for-human-respiratory-syncytial-virus-ns1-mediated-modulation-of-host-responses
#16
Srirupa Chatterjee, Priya Luthra, Ekaterina Esaulova, Eugene Agapov, Benjamin C Yen, Dominika M Borek, Megan R Edwards, Anuradha Mittal, David S Jordan, Parameshwar Ramanan, Martin L Moore, Rohit V Pappu, Michael J Holtzman, Maxim N Artyomov, Christopher F Basler, Gaya K Amarasinghe, Daisy W Leung
Human respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the paediatric, elderly and immune-compromised populations(1,2). A gap in our understanding of hRSV disease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists(3-6); however, the role of these proteins in viral pathogenesis is incompletely understood. Here, we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralogue of hRSV matrix (M) protein...
June 30, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28659900/efficacy-of-live-attenuated-h9n2-influenza-vaccine-candidates-containing-ns1-truncations-against-h9n2-avian-influenza-viruses
#17
Sujuan Chen, Yinbiao Zhu, Da Yang, Yang Yang, Shaohua Shi, Tao Qin, Daxin Peng, Xiufan Liu
H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28659477/west-nile-virus-ns1-antagonizes-interferon-%C3%AE-production-by-targeting-rig-i-and-mda5
#18
Hong-Lei Zhang, Han-Qing Ye, Si-Qing Liu, Cheng-Lin Deng, Xiao-Dan Li, Pei-Yong Shi, Bo Zhang
West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has posed significant a public health threat since the outbreak in New York City in 1999. The interferon (IFN)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. Previous studies have suggested that multifunctional non-structural proteins encoded by flaviviruses antagonize the host IFN response via various means in order to establish efficient viral replication...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28654045/rescue-and-characterization-of-recombinant-virus-from-a-new-world-zika-virus-infectious-clone
#19
James Weger-Lucarelli, Nisha K Duggal, Aaron C Brault, Brian J Geiss, Gregory D Ebel
Infectious cDNA clones allow for genetic manipulation of a virus, thus facilitating work on vaccines, pathogenesis, replication, transmission and viral evolution. Here we describe the construction of an infectious clone for Zika virus (ZIKV), which is currently causing an explosive outbreak in the Americas. To prevent toxicity to bacteria that is commonly observed with flavivirus-derived plasmids, we generated a two-plasmid system which separates the genome at the NS1 gene and is more stable than full-length constructs that could not be successfully recovered without mutations...
June 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28648850/complete-genome-analysis-of-dengue-virus-type-3-isolated-from-the-2013-dengue-outbreak-in-yunnan-china
#20
Xiaodan Wang, Dehong Ma, Xinwei Huang, Lihua Li, Duo Li, Yujiao Zhao, Lijuan Qiu, Yue Pan, Junying Chen, Juemin Xi, Xiyun Shan, Qiangming Sun
In the past few decades, dengue has spread rapidly and is an emerging disease in China. An unexpected dengue outbreak occurred in Xishuangbanna, Yunnan, China, resulting in 1331 patients in 2013. In order to obtain the complete genome information and perform mutation and evolutionary analysis of causative agent related to this largest outbreak of dengue fever. The viruses were isolated by cell culture and evaluated by genome sequence analysis. Phylogenetic trees were then constructed by Neighbor-Joining methods (MEGA6...
June 23, 2017: Virus Research
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