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https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#1
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27914808/influenza-a-virus-ns1-protein-induced-a20-contributes-to-viral-replication-by-suppressing-interferon-induced-antiviral-response
#2
Wenjing Feng, Xiaoning Sun, Ning Shi, Maolin Zhang, Zhenhong Guan, Ming Duan
The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. A20 is a cytoplasmic ubiquitin-editing protein that negatively regulates the retinoic acid-inducible gene I (RIG-I)-mediated activation of interferon regulatory factors (IRF) 3. Here, we found that influenza A virus (IAV) non-structural protein (NS) 1 dramatically induced the protein level of A20 in A549 cells whose expression levels were positively associated with the viral virulence...
December 1, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27902334/the-ns1-protein-of-avian-influenza-virus-h9n2-induces-oxidative-stress-mediated-chicken-oviduct-epithelial-cells-coecs-apoptosis
#3
Xuefeng Qi, Huizhu Zhang, Qiuzhen Wang, Jingyu Wang
The pathogenesis of H9N2 subtype avian influenza virus infection (AIV) in the hens is often related to the oviduct tissue damage. The viral nonstructural NS1 protein is thought to play key role in regulating the pathogenicity of AIV, but the exact function to this process remains elusive. In this study, the pro-apoptosis effect of H9N2 NS1 protein was examined on chicken oviduct epithelial cells (COECs) and our data suggested that NS1 induced oxidative stress was a contributing factor for apoptosis. Our data suggest that NS1 protein level was correlated with reactive oxygen species (ROS) in COECs cells transfected with NS1 expression plasmids...
October 20, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27869202/suppression-of-rac1-signaling-by-influenza-a-virus-ns1-facilitates-viral-replication
#4
Wei Jiang, Chunjie Sheng, Xiuling Gu, Dong Liu, Chen Yao, Shijuan Gao, Shuai Chen, Yinghui Huang, Wenlin Huang, Min Fang
Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27867373/two-genetically-similar-h9n2-influenza-a-viruses-show-different-pathogenicity-in-mice
#5
Qingtao Liu, Yuzhuo Liu, Jing Yang, Xinmei Huang, Kaikai Han, Dongmin Zhao, Keran Bi, Yin Li
H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD50) of 10(2.83) 50% egg infectious dose (EID50), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD50 of >10(6...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27860276/regulation-of-kynurenine-biosynthesis-during-influenza-virus-infection
#6
Lana Gaelings, Sandra Söderholm, Andrii Bugai, Yu Fu, Jatin Nandania, Bert Schepens, Martina B Lorey, Janne Tynell, Liesbeth Vande Ginste, Ronan Le Goffic, Matthew S Miller, Marika Kuisma, Varpu Marjomäki, Jef De Brabander, Sampsa Matikainen, Tuula A Nyman, Dennis Bamford, Xavier Saelens, Ilkka Julkunen, Henrik Paavilainen, Veijo Hukkanen, Vidya Velagapudi, Denis E Kainov
Influenza A viruses (IAVs) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus-host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T-cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis...
November 18, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27846859/attenuation-of-the-virulence-of-a-recombinant-influenza-virus-expressing-the-naturally-truncated-ns-gene-from-an-h3n8-equine-influenza-virus-in-mice
#7
Woonsung Na, Kwang-Soo Lyoo, Sun-Woo Yoon, Minjoo Yeom, Bokyu Kang, Hyoungjoon Moon, Hye Kwon Kim, Dae Gwin Jeong, Jeong-Ki Kim, Daesub Song
Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids. Recently, we isolated an H3N8 EIV (A/equine/Kyonggi/SA1/2011) from a domestic horse in South Korea that exhibited symptoms of respiratory disease, and found that the EIV strain contained a naturally mutated NS gene segment encoding a truncated NS1 protein. In order to determine whether there was an association between the NS gene truncation and viral virulence, a reverse genetics system was applied to generate various NS gene recombinant viruses using the backbone of the H1N1 A/Puerto Rico/8/1934 (PR/8) virus...
November 15, 2016: Veterinary Research
https://www.readbyqxmd.com/read/27814373/involvement-of-an-arginine-triplet-in-m1-matrix-protein-interaction-with-membranes-and-in-m1-recruitment-into-virus-like-particles-of-the-influenza-a-h1n1-pdm09-virus
#8
Adeline Kerviel, Shantoshini Dash, Olivier Moncorgé, Baptiste Panthu, Jan Prchal, Didier Décimo, Théophile Ohlmann, Bruno Lina, Cyril Favard, Etienne Decroly, Michèle Ottmann, Philippe Roingeard, Delphine Muriaux
The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5...
2016: PloS One
https://www.readbyqxmd.com/read/27807230/zaps-inhibits-influenza-a-viral-protein-expression-and-is-antagonized-by-the-virus-encoded-ns1
#9
Qiannan Tang, Xinlu Wang, Guangxia Gao
: Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses. There are two ZAP isoforms arising from alternative splicing, which differ only at the C-termini. It was recently reported that the long isoform (ZAPL) promotes proteasomal degradation of influenza A virus (IAV) proteins PA and PB2 through the C-terminal PARP-domain, which is missing in the short form (ZAPS), and that this antiviral activity is antagonized by the viral protein PB1...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27807226/subcellular-localizations-of-rig-i-trim25-and-mavs-complexes
#10
M T Sánchez-Aparicio, J Ayllón, A Leo-Macias, T Wolff, A García-Sastre
: The RIG-I signaling pathway is essential for the recognition of viruses and the initiation of host IFN-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds MAVS, leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway, through the use of Bimolecular Fluorescence Complementation (BiFC) and super resolution microscopy. Dimers of RIG-I, TRIM25 and MAVS localize into different compartments...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27788253/repurposed-transcriptomic-data-reveal-small-viral-rna-produced-by-influenza-virus-during-infection-in-mice
#11
Amanda Koire, Brian E Gilbert, Richard Sucgang, Lynn Zechiedrich
Influenza virus, a highly infectious ssRNA virus, replicates in the nucleus of host cells. This unusual feature brings the possibility that the virus may hijack host small noncoding RNA metabolism. Influenza small viral RNA production has been examined in vitro but has not yet been studied in an in vivo setting. We assessed small RNA species from influenza virus during mouse infection by mining publicly available mouse small RNA transcriptome data. We uncovered 26 nt reads corresponding to svRNA, a small viral RNA previously detected in vitro that regulates the transition from transcription to replication during infection, and found a strong positive correlation between svRNA production and host susceptibility to influenza virus infection...
2016: PloS One
https://www.readbyqxmd.com/read/27750071/canine-influenza-viruses-with-modified-ns1-proteins-for-the-development-of-live-attenuated-vaccines
#12
Aitor Nogales, Kai Huang, Caroline Chauché, Marta L DeDiego, Pablo R Murcia, Colin R Parrish, Luis Martínez-Sobrido
Canine Influenza Virus (CIV) H3N8 is the causative agent of canine influenza, a common and contagious respiratory disease of dogs. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV H3N8. However, live-attenuated influenza vaccines (LAIVs) are known to provide better immunogenicity and protection efficacy than IIVs. Influenza NS1 is a virulence factor that offers an attractive target for the preparation of attenuated viruses as LAIVs. Here we generated recombinant H3N8 CIVs containing truncated or a deleted NS1 protein to test their potential as LAIVs...
October 14, 2016: Virology
https://www.readbyqxmd.com/read/27718266/the-influenza-a-virus-nonstructural-protein-ns1-up-regulates-the-expression-of-collagen-triple-helix-repeat-containing-1-protein
#13
Chengliang Zhu, Guiqing Peng, Wei Yi, Hui Song, Fang Liu, Xinghui Liu
Influenza A virus (IAV) infection induces a strong immune response and regulates the expression of many host proteins. The collagen triple helix repeat containing 1 (CTHRC1) protein is a secreted protein that exhibits increased expression during the viral infection process. However, the regulatory function of IAV on CTHRC1 expression is obscure. In this study, we investigated the effect of IAV on CTHRC1 expression and its regulatory mechanism. A total of 106 serum specimens from healthy people and 80 serum specimens from patients infected with IAV were collected...
October 8, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27687232/mda7-il-24-is-an-anti-viral-factor-that-inhibits-influenza-virus-replication
#14
Rak-Kyun Seong, Young-Ki Choi, Ok Sarah Shin
Melanoma differentiation associated gene-7 (mda-7)/interleukin- 24 (IL-24) is a secreted cytokine, which plays an essential role in tumor suppression. Although its role as a multifunctional protein affecting broad types of cancers is well described, functions of IL-24 in host defense against virus infection are yet to be determined. In this study, we explored the anti-viral effect of recombinant IL-24 treatment during influenza infection. Infection of human lung adenocarcinoma cells (A549) with the influenza A virus up-regulated IL-24 mRNA and protein expression in a time-dependent manner...
October 2016: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/27664935/influenza-virus-ns1-protein-binds-cellular-dna-to-block-transcription-of-antiviral-genes
#15
Maria Anastasina, Nicolas Le May, Andrii Bugai, Yu Fu, Sandra Söderholm, Lana Gaelings, Tiina Ohman, Janne Tynell, Suvi Kyttänen, Matjaz Barboric, Tuula A Nyman, Sampsa Matikainen, Ilkka Julkunen, Sarah J Butcher, Jean-Marc Egly, Denis E Kainov
Influenza NS1 protein is an important virulence factor that is capable of binding double-stranded (ds) RNA and inhibiting dsRNA-mediated host innate immune responses. Here we show that NS1 can also bind cellular dsDNA. This interaction prevents loading of transcriptional machinery to the DNA, thereby attenuating IAV-mediated expression of antiviral genes. Thus, we identified a previously undescribed strategy, by which RNA virus inhibits cellular transcription to escape antiviral response and secure its replication...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27664027/g45r-on-nonstructural-protein-1-of-influenza-a-virus-contributes-to-virulence-by-increasing-the-expression-of-proinflammatory-cytokines-in-mice
#16
Challika Kaewborisuth, Bryan Kaplan, Mark Zanin, David Finkelstein, Richard J Webby, Porntippa Lekcharoensuk
Nonstructural protein 1 (NS1) is a multifunctional protein that is a viral replication enhancer and virulence factor. In this study, we investigated the effect of the amino acid substitution G45R on the NS1 of A/Puerto Rico/8/1934 (H1N1) (G45R/NS1) on viral virulence and host gene expression in a mouse model and the human lung cell line A549. The G45R/NS1 virus had increased virulence by inducing an earlier and robust proinflammatory cytokine response in mice. Mice infected with the G45R/NS1 virus lost more body weight and had lower survival rates than mice infected with the wild type (WT/NS1) virus...
September 23, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27663652/amino-acid-substitutions-involved-in-the-adaptation-of-a-novel-highly-pathogenic-h5n2-avian-influenza-virus-in-mice
#17
Haibo Wu, Xiuming Peng, Xiaorong Peng, Nanping Wu
BACKGROUND: H5N2 avian influenza viruses (AIVs) can infect individuals that are in frequent contact with infected birds. In 2013, we isolated a novel reassortant highly pathogenic H5N2 AIV strain [A/duck/Zhejiang/6DK19/2013(H5N2) (6DK19)] from a duck in Eastern China. This study was undertaken to understand the adaptive processes that led enhanced replication and increased virulence of 6DK19 in mammals. 6DK19 was adapted to mice using serial lung-to-lung passages (10 passages total). The virulence of the wild-type virus (WT-6DK19) and mouse-adapted virus (MA-6DK19) was determined in mice...
2016: Virology Journal
https://www.readbyqxmd.com/read/27633136/biochemical-and-structural-characterization-of-the-interface-mediating-interaction-between-the-influenza-a-virus-non-structural-protein-1-and-a-monoclonal-antibody
#18
Jianping Wu, Chee-Keng Mok, Vincent Tak Kwong Chow, Y Adam Yuan, Yee-Joo Tan
We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27589809/the-influenza-ns1-protein-what-do-we-know-in-equine-influenza-virus-pathogenesis
#19
REVIEW
Marta Barba, Janet M Daly
Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1) has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon...
August 31, 2016: Pathogens
https://www.readbyqxmd.com/read/27572970/influenza-virus-mrna-trafficking-through-host-nuclear-speckles
#20
Amir Mor, Alexander White, Ke Zhang, Matthew Thompson, Matthew Esparza, Raquel Muñoz-Moreno, Kazunori Koide, Kristen W Lynch, Adolfo García-Sastre, Beatriz M A Fontoura
Influenza A virus is a human pathogen with a genome composed of eight viral RNA segments that replicate in the nucleus. Two viral mRNAs are alternatively spliced. The unspliced M1 mRNA is translated into the matrix M1 protein, while the ion channel M2 protein is generated after alternative splicing. These proteins are critical mediators of viral trafficking and budding. We show that the influenza virus uses nuclear speckles to promote post-transcriptional splicing of its M1 mRNA. We assign previously unknown roles for the viral NS1 protein and cellular factors to an intranuclear trafficking pathway that targets the viral M1 mRNA to nuclear speckles, mediates splicing at these nuclear bodies and exports the spliced M2 mRNA from the nucleus...
2016: Nature Microbiology
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