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influenza ns1

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
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
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
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...
September 21, 2016: Biochimica et Biophysica Acta
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
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
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
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
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
Li-Chung Ma, Rongjin Guan, Keith Hamilton, James M Aramini, Lei Mao, Shanshan Wang, Robert M Krug, Gaetano T Montelione
Influenza viruses cause a highly contagious respiratory disease in humans. The NS1 proteins of influenza A and B viruses (NS1A and NS1B proteins, respectively) are composed of two domains, a dimeric N-terminal domain and a C-terminal domain, connected by a flexible polypeptide linker. Here we report the 2.0-Å X-ray crystal structure and nuclear magnetic resonance studies of the NS1B C-terminal domain, which reveal a novel and unexpected basic RNA-binding site that is not present in the NS1A protein. We demonstrate that single-site alanine replacements of basic residues in this site lead to reduced RNA-binding activity, and that recombinant influenza B viruses expressing these mutant NS1B proteins are severely attenuated in replication...
September 6, 2016: Structure
Marta L DeDiego, Aitor Nogales, Kris Lambert-Emo, Luis Martinez-Sobrido, David J Topham
: Influenza NS1 protein is the main viral protein counteracting host innate immune responses, allowing the virus to efficiently replicate in interferon (IFN)-competent systems. In this study, we analyzed NS1 protein variability within influenza A (IAV) H3N2 viruses infecting humans during the 2012-2013 season. We also evaluated the impact of the mutations on the ability of NS1 proteins to inhibit host innate immune responses and general gene expression. Surprisingly, a previously unidentified mutation in the double-stranded RNA (dsRNA)-binding domain (I64T) decreased NS1-mediated general inhibition of host protein synthesis by decreasing its interaction with cleavage and polyadenylation specificity factor 30 (CPSF30), leading to increased innate immune responses after viral infection...
November 1, 2016: Journal of Virology
Matthew L Turnbull, Helen M Wise, Marlynne Q Nicol, Nikki Smith, Rebecca L Dunfee, Philippa M Beard, Brett W Jagger, Yvonne Ligertwood, Gareth R Hardisty, Haixia Xiao, Donald J Benton, Alice M Coburn, Joao A Paulo, Steven P Gygi, John W McCauley, Jeffery K Taubenberger, Samantha J Lycett, Michael P Weekes, Bernadette M Dutia, Paul Digard
UNLABELLED: Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types...
October 15, 2016: Journal of Virology
Zeeshan Khaliq, Mikael Leijon, Sándor Belák, Jan Komorowski
BACKGROUND: The underlying strategies used by influenza A viruses (IAVs) to adapt to new hosts while crossing the species barrier are complex and yet to be understood completely. Several studies have been published identifying singular genomic signatures that indicate such a host switch. The complexity of the problem suggested that in addition to the singular signatures, there might be a combinatorial use of such genomic features, in nature, defining adaptation to hosts. RESULTS: We used computational rule-based modeling to identify combinatorial sets of interacting amino acid (aa) residues in 12 proteins of IAVs of H1N1 and H3N2 subtypes...
2016: BMC Genomics
Michaela Weber-Gerlach, Friedemann Weber
The nonstructural protein NS1 is well established as a virulence factor of influenza A virus counteracting induction of the antiviral type I interferon system. Recent studies now show that viral structural proteins, their derivatives, and even the genome itself also contribute to keeping the host defense under control. Here, we summarize the current knowledge on these NS1-independent interferon escape strategies.
October 1, 2016: Journal of Virology
Matteo Samuele Pizzuto, Micol Silic-Benussi, Vincenzo Ciminale, Ruth A Elderfield, Ilaria Capua, Wendy S Barclay
Pancreatic ductal adenocarcinoma (PDA) is one of the leading causes of cancer-related deaths worldwide and the development of new treatment strategies for PDA patients is of crucial importance. Virotherapy uses natural or engineered oncolytic viruses (OVs) to selectively kill tumour cells. Due to their genetic heterogeneity, PDA cells are highly variable in their permissiveness to various OVs. The avian influenza A virus (IAV) H7N3 A/turkey/Italy/2962/03 is a potent inducer of apoptosis in PDA cells previously shown to be resistant to other OVs (Kasloff et al...
September 2016: Journal of General Virology
Pumaree Kanrai, Ahmed Mostafa, Ramakanth Madhugiri, Marcus Lechner, Esther Wilk, Klaus Schughart, Leena Ylösmäki, Kalle Saksela, John Ziebuhr, Stephan Pleschka
Reassortment of their segmented genomes allows influenza A viruses (IAV) to gain new characteristics, which potentially enable them to cross the species barrier and infect new hosts. Improved replication was observed for reassortants of the strictly avian IAV A/FPV/Rostock/34 (FPV, H7N1) containing the NS segment from A/Goose/Guangdong/1/1996 (GD, H5N1), but not for reassortants containing the NS segment of A/Mallard/NL/12/2000 (MA, H7N3). The NS1 of GD and MA differ only in 8 aa positions. Here, we show that efficient replication of FPV-NSMA-derived mutants was linked to the presence of a single substitution (D74N) and more prominently to a triple substitution (P3S+R41K+D74N) in the NS1MA protein...
September 2016: Journal of General Virology
Challika Kaewborisuth, Mark Zanin, Hans Häcker, Richard J Webby, Porntippa Lekcharoensuk
BACKGROUND: The nonstructural protein 1 (NS1) of influenza A viruses can act as a viral replication enhancer by antagonizing type I interferon (IFN) induction and response in infected cells. We previously reported that A/Puerto Rico/8/1934 (H1N1) (PR8) containing the NS1 gene derived from A/swine/IA/15/1930 (H1N1) (IA30) replicated more efficiently than the wild type virus. Here, we identified amino acids in NS1 critical for enhancing viral replication. METHODS: To identify a key amino acid in NS1 which can increase the virus replication, growth kinetics of PR8 viruses encoding single mutation in NS1 were compared in A549 cells...
2016: Virology Journal
Jihye Lee, Ji Hoon Park, Ji-Young Min
The non-structural protein of influenza A virus (NS1A protein) is a multifunctional protein that antagonizes host antiviral responses and contributes to efficient viral replication during infection. However, most of its functions have been elucidated by generating recombinant viruses expressing mutated NS1 proteins that do not exist in nature. Recently, the novel H3N8 A/Equine/Kyonggi/SA1/2011 (KG11) influenza virus was isolated in Korea from horses showing respiratory disease symptoms. KG11 virus contains a naturally truncated NS gene segment with the truncation in the NS1A coding region, resulting in truncation of the effector domain of the NS1A protein...
July 11, 2016: Archives of Virology
Weinan Zheng, Shuaishuai Cao, Can Chen, Jing Li, Shuang Zhang, Jingwen Jiang, Yange Niu, Wenhui Fan, Yun Li, Yuhai Bi, Lei Sun, George F Gao, Wenjun Liu
Influenza A virus evades host antiviral defense through hijacking innate immunity by its nonstructural protein 1 (NS1). By using mass spectrometry, threonine 80 (T80) was identified as a novel phosphorylated residue in the NS1 of the influenza virus A/WSN/1933(H1N1). By generating recombinant influenza viruses encoding NS1 T80 mutants, the roles of this phosphorylation site were characterized during viral replication. The T80E (phosphomimetic) mutant attenuated virus replication, whereas the T80A (non-phosphorylatable) mutant did not...
July 4, 2016: Cellular Microbiology
Emad Mohamed Elgendy, Yohei Watanabe, Tomo Daidoji, Yasuha Arai, Kazuyoshi Ikuta, Madiha Salah Ibrahim, Takaaki Nakaya
Avian influenza viruses impose serious public health burdens with significant mortality and morbidity not only in poultry but also in humans. While poultry susceptibility to avian influenza virus infection is well characterized, pigeons have been thought to have low susceptibility to these viruses. However, recent studies reported natural pigeon infections with highly pathogenic avian influenza H5N1 viruses. In Egypt, which is one of the H5N1 endemic areas for birds, pigeons are raised in towers built on farms in backyards and on house roofs, providing a potential risk for virus transmission from pigeons to humans...
July 1, 2016: Virus Genes
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