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influenza ns1

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https://www.readbyqxmd.com/read/28554059/residues-f103-and-m106-within-the-influenza-a-virus-ns1-cpsf4-binding-region-regulate-interferon-stimulated-gene-translation-initiation
#1
Ben X Wang, Earl G Brown, Eleanor N Fish
Influenza A virus (IAV) non-structural protein 1 (NS1) suppresses host innate immune responses by inhibiting type I interferon (IFN) production. We provide evidence that residues F103 and M106 in the CPSF4-binding domain of A/HK/1/68 [H3N2] NS1 contribute to post-transcriptional inhibition of antiviral IFN-stimulated genes (ISGs), thereby suppressing an antiviral type I IFN response. Recombinant (r) IAVs encoding F103L and M106I mutations in NS1 replicate to significantly lower viral titers in human A549 lung epithelial cells and primary type II alveolar cells...
May 26, 2017: Virology
https://www.readbyqxmd.com/read/28515301/the-influenza-a-virus-ns1-protein-promotes-efficient-nuclear-export-of-unspliced-viral-m1-mrna
#2
Carina F Pereira, Eliot K C Read, Helen M Wise, Maria J Amorim, Paul Digard
Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality control checkpoints...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514196/interactions-between-ns1-of-influenza-a-viruses-and-interferon-%C3%AE-%C3%AE-determinants-for-vaccine-development
#3
Ben X Wang, Eleanor N Fish
Influenza A viruses (IAVs) cause mild to severe infections in humans with considerable socioeconomic and global health consequences. The host interferon (IFN)-α/β response, critical as the first line of defense against foreign pathogens, is induced upon detection of IAV genomic RNA in infected cells by host innate pattern recognition receptors. IFN-α/β production and subsequent activation of cell signaling result in the expression of antiviral IFN-stimulated genes whose products target various stages of the IAV life cycle to inhibit viral replication and the spread of infection and establish an antiviral state...
May 17, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28498306/a-conserved-residue-tyrosine-y-84-in-h5n1-influenza-a-virus-ns1-regulates-ifn-signaling-responses-to-enhance-viral-infection
#4
Ben X Wang, Lianhu Wei, Lakshmi P Kotra, Earl G Brown, Eleanor N Fish
The non-structural protein, NS1, is a virulence factor encoded by influenza A viruses (IAVs). In this report, we provide evidence that the conserved residue, tyrosine (Y) 84, in a conserved putative SH2-binding domain in A/Duck/Hubei/2004/L-1 [H5N1] NS1 is critical for limiting an interferon (IFN) response to infection. A phenylalanine (F) substitution of this Y84 residue abolishes NS1-mediated downregulation of IFN-inducible STAT phosphorylation, and surface IFNAR1 expression. Recombinant IAV (rIAV) [H1N1] expressing A/Grey Heron/Hong Kong/837/2004 [H5N1] NS1-Y84F (rWSN-GH-NS1-Y84F) replicates to lower titers in human lung epithelial cells and is more susceptible to the antiviral effects of IFN-β treatment compared with rIAV expressing the intact H5N1 NS1 (rWSN-GH-NS1-wt)...
May 12, 2017: Viruses
https://www.readbyqxmd.com/read/28481988/generation-and-characterization-of-monoclonal-antibodies-against-the-ns1-protein-of-h17n10-bat-influenza-virus
#5
Junna Gao, Kaidi Xu, Haiwei Sun, Qinfang Liu, Jianmei Yang, Qiaoyang Teng, Xuesong Li, Zhaoguo Chen, Zejun Li, Hongjun Chen
No abstract text is available yet for this article.
May 8, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28433538/the-ns1-protein-from-influenza-virus-stimulates-translation-initiation-by-enhancing-ribosome-recruitment-to-mrnas
#6
Baptiste Panthu, Olivier Terrier, Coralie Carron, Aurélien Traversier, Antoine Corbin, Laurent Balvay, Bruno Lina, Manuel Rosa-Calatrava, Théophile Ohlmann
The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Amongst these functions, NS1 was shown to be involved both in the control of viral and cellular translation; however the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses IRESes (DCV and CrPV), suggesting a role at the level of translation initiation...
April 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28426973/non-linear-enhancement-of-mrna-delivery-efficiencies-by-influenza-a-derived-ns1-protein-engendering-host-gene-inhibition-property
#7
Kyle K L Phua, Yi Liu, Shun Hui Sim
Nucleic acid induced immunogenicity remains a significant impediment in biomedical therapeutics because the innate immune system is a complex network overlaid with functional redundancies. Herein we report that non-structural protein 1 (NS1), an immune evasion protein derived from influenza A virus, when co-delivered in mRNA format is a potent mRNA transfection enhancer without toxicity. Transfection enhancement is mediated by NS1's effector domain through inhibition of IRF3 and PKR, activators of early anti-viral responses as well as CPSF30, a non immunostimulating protein...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28400751/ethanolic-extract-of-melia-fructus-has-anti-influenza-a-virus-activity-by-affecting-viral-entry-and-viral-rna-polymerase
#8
Young-Hee Jin, Jang-Gi Choi, Won-Kyung Cho, Jin Yeul Ma
Meliae Fructus (MF) is the dried ripe fruit of Melia toosendan Siebold et Zuccarini, Meliaceae family. MF is widely used in traditional medicine to treat inflammation and helminthic infection and has anti-bacterial, anti-oxidant, anti-cancer, anti-inflammatory, and analgesic activities. However, potential anti-influenza properties of MF have yet to be investigated. We determined whether an ethanolic extract of MF (EMF) has anti-viral activity via an EMF pre-, co-, and post-treatment assay, using the Influenza A/PR/8/34 and H3N2 virus on Madin-Darby canine kidney (MDCK) cells...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28395999/the-ns1-protein-of-h5n6-feline-influenza-virus-inhibits-feline-beta-interferon-response-by-preventing-nf-%C3%AE%C2%BAb-and-irf3-activation
#9
Lifang Wang, Xinliang Fu, Yun Zheng, Pei Zhou, Bo Fang, San Huang, Xin Zhang, Jidang Chen, Zongxi Cao, Jin Tian, Shoujun Li
Despite the apparent lack of a feline influenza virus lineage, cats are susceptible to infection by influenza A viruses. Here, we characterized in vitro A/feline/Guangdong/1/2015, an H5N6 avian influenza virus recently isolated from cats. A/feline/Guangdong/1/2015 replicated to high titers and caused CPE in feline kidney cells. We determined that infection with A/feline/Guangdong/1/2015 did not activate the IFN-β promoter, but inhibited it by blocking the activation of NF-κB and IRF3. We also determined that the viral NS1 protein mediated the block, and that the dsRNA binding domain of NS1 was essential to perform this function...
April 7, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28370088/expression-of-surface-bound-nonstructural-1-ns1-protein-of-influenza-virus-a-h5n1-on-lactobacillus-casei-strain-c1
#10
T S Tan, S Syed Hassan, W B Yap
The study aimed to construct a recombinant Lactobacillus casei expressing the nonstructural (NS) 1 protein of influenza A virus H5N1 on its cell wall. The NS1 gene was first amplified and fused to the pSGANC332 expression plasmid. The NS1 protein expression was carried out by Lact. casei strain C1. PCR screening and DNA sequencing confirmed the presence of recombinant pSG-NS1-ANC332 plasmid in Lact. casei. The plasmid was stably maintained (98·94 ± 1·65%) by the bacterium within the first 20 generations without selective pressure...
June 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/28368102/the-molecular-mechanisms-underlying-the-hijack-of-host-proteins-by-the-1918-spanish-influenza-virus
#11
Qingliang Shen, Danyun Zeng, Baoyu Zhao, Veer S Bhatt, Pingwei Li, Jae-Hyun Cho
The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster kon and 3300-fold lower Kd compared to those for the CrkII-JNK1 interaction...
April 5, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28348873/molecular-and-biochemical-characterization-of-the-ns1-protein-of-non-cultured-influenza-b-virus-strains-circulating-in-singapore
#12
Muhammad Raihan Jumat, Puisan Wong, Raphael Tze Chuen Lee, Sebastian Maurer-Stroh, Boon Huan Tan, Richard J Sugrue
In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92-93), and that p23 contained the first 92 amino acids of the NS1 protein...
August 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28323816/an-ns-segment-exonic-splicing-enhancer-regulates-influenza-a-virus-replication-in-mammalian-cells
#13
Xiaofeng Huang, Min Zheng, Pui Wang, Bobo Wing-Yee Mok, Siwen Liu, Siu-Ying Lau, Pin Chen, Yen-Chin Liu, Honglian Liu, Yixin Chen, Wenjun Song, Kwok-Yung Yuen, Honglin Chen
Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2-ESE interaction...
March 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28250123/influenza-a-virus-virulence-depends-on-two-amino-acids-in-the-n-terminal-domain-of-its-ns1-protein-to-facilitate-inhibition-of-the-rna-dependent-protein-kinase-pkr
#14
Kristina L Schierhorn, Fabian Jolmes, Julia Bespalowa, Sandra Saenger, Christin Peteranderl, Julia Dzieciolowski, Maja Mielke, Matthias Budt, Stephan Pleschka, Andreas Herrmann, Susanne Herold, Thorsten Wolff
The RNA-dependent protein kinase (PKR) has broad antiviral activity inducing translational shutdown of viral and cellular genes and is therefore targeted by various viral proteins to facilitate pathogen propagation. The pleiotropic NS1 protein of influenza A virus acts as silencer of PKR activation and ensures high-level viral replication and virulence. However, the exact manner of this inhibition remains controversial. To elucidate the structural requirements within the NS1 protein for PKR inhibition, we generated a set of mutant viruses, identifying highly conserved arginine residues 35 and 46 within the NS1 N terminus as being most critical not only for binding to and blocking activation of PKR but also for efficient virus propagation...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202040/subcellular-localization-and-interactions-of-infectious-salmon-anemia-virus-isav-m1-and-nep-as-well-as-host-hsc70
#15
Wenting Zhang, Chengzhi Cai, Li Lin, Yizhi Jane Tao, Meilin Jin
BACKGROUND: Infectious salmon anemia virus (ISAV) is an important fish pathogen that causes high mortality in farmed Atlantic salmon. The ISAV genome consists of eight single-stranded, negative-sense RNA segments. The six largest segments contain one open reading frame (ORF) each, and encode three polymerase proteins, nucleoprotein, fusion protein, and hemagglutinin esterase protein. The two smallest segments contain more than one ORF each. The segment 7 encodes non-structural protein 1 (NS1) and nuclear export protein (NEP), while segment 8 encodes matrix protein 1 and 2 (M1 and M2)...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28148793/mutations-during-the-adaptation-of-h9n2-avian-influenza-virus-to-the-respiratory-epithelium-of-pigs-enhance-sialic-acid-binding-activity-and-virulence-in-mice
#16
W Yang, D Punyadarsaniya, R L O Lambertz, D C C Lee, C H Liang, D Höper, S R Leist, A Hernández-Cáceres, J Stech, M Beer, C Y Wu, C H Wong, K Schughart, F Meng, G Herrler
The natural reservoir for influenza viruses is waterfowl, and from there they succeeded in crossing the barrier to different mammalian species. We analyzed the adaptation of avian influenza viruses to a mammalian host by passaging an H9N2 strain three times in differentiated swine airway epithelial cells. Using precision-cut slices from the porcine lung to passage the parental virus, isolates from each of the three passages (P1 to P3) were characterized by assessing growth curves and ciliostatic effects. The only difference noted was an increased growth kinetics of the P3 virus...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28110426/influenza-a-virus-upregulates-prpf8-gene-expression-to-increase-virus-production
#17
Chee-Hing Yang, Hui-Chun Li, Yu-Ling Shiu, Tzu-Shan Ku, Chia-Wen Wang, Yi-Shuan Tu, Hung-Ling Chen, Cheng-Hao Wu, Shih-Yen Lo
A ddRT-PCR analysis was performed to detect cellular genes that are differentially expressed after influenza A virus (H1N1) infection of A549 cells. After ddRT-PCR, eight DNA fragments were identified. PRPF8, one of the cellular genes that were upregulated after virus infection, was further analyzed since it has previously been identified as a cellular factor required for influenza virus replication. The upregulation of PRPF8 gene expression after viral infection was confirmed using real-time RT-PCR for mRNA detection and Western blot analysis for protein detection...
May 2017: Archives of Virology
https://www.readbyqxmd.com/read/28076660/influenza-a-virus-ns1-protein-induced-jnk-activation-and-apoptosis-are-not-functionally-linked
#18
Wolfgang Nacken, Viktor Wixler, Christina Ehrhardt, Stephan Ludwig
Expression of the influenza A virus (IAV) nonstructural protein (NS1) results in the activation of c-Jun N-terminal kinase (JNK). Both NS1 and JNK are involved in apoptosis induction. To investigate their interrelationship, we stably expressed a tamoxifen inducible NS1 oestrogen receptor fusion-protein (NS1ERT) in mammalian cells. Upon tamoxifen stimulation, NS1ERT-expressing cells partially rescued the attenuated replication of NS1-deficient IAVs and also inhibited interferon up-regulation, confirming the functional competence of NS1ERT...
January 11, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28003482/ns1-protein-amino-acid-changes-d189n-and-v194i-affect-interferon-responses-thermosensitivity-and-virulence-of-circulating-h3n2-human-influenza-a-viruses
#19
Aitor Nogales, Luis Martinez-Sobrido, David J Topham, Marta L DeDiego
Influenza virus NS1 protein is a nonstructural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. NS1 protein variability in subjects infected with H3N2 influenza A viruses (IAVs) during the 2010/2011 season was analyzed, and amino acid changes in residues 86, 189, and 194 were found. The consequences of these mutations for the NS1-mediated inhibition of IFN responses and the pathogenesis of the virus were evaluated, showing that NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, most probably because these mutations decreased the binding of NS1 to the cleavage and polyadenylation specificity factor 30 (CPSF30)...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27983470/single-cell-studies-of-ifn-%C3%AE-promoter-activation-by-wild-type-and-ns1-defective-influenza-a-viruses
#20
M J Killip, D Jackson, M Pérez-Cidoncha, E Fodor, R E Randall
Deletion or truncation of NS1, the principal IFN antagonist of influenza viruses, leads to increased IFN induction during influenza virus infection. We have studied activation of the IFN induction cascade by both wild-type and NS1-defective viruses at the single-cell level using a cell line expressing GFP under the control of the IFN-β promoter and by examining MxA expression. The IFN-β promoter was not activated in all infected cells even during NS1-defective virus infections. Loss of NS1 expression is therefore insufficient per se to induce IFN in an infected cell, and factors besides NS1 expression status must dictate whether the IFN response is activated...
March 2017: Journal of General Virology
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