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influenza ns1

Jing Li, Kun Zhang, Quanjiao Chen, Xiaoshuang Zhang, Yeping Sun, Yuhai Bi, Shuang Zhang, Jinyan Gu, Jiarong Li, Di Liu, Wenjun Liu, Jiyong Zhou
Influenza A viruses have sophisticated strategies to promote their own replication. Here, we found that three H5N1 influenza viruses display different replication patterns in human A549 and macrophage cells. The HN01 virus displayed poor replication compared to HN021 and JS01. In addition, the HN01 virus was unable to counteract the interferon response and block general gene expression. This capability was restored by three amino acid substitutions on the NS1 protein: K55E, K66E, and C133F, resulting in recovered binding to CPSF30 and decreased interferon response activity...
April 17, 2018: Virology
Jinping Li, Guangyu Hou, Yan Wang, Suchun Wang, Cheng Peng, Xiaohui Yu, Wenming Jiang
The H5 and H7N9 subtypes of highly pathogenic avian influenza viruses (HPAIVs) in China pose a serious challenge to public health and the poultry industry. In this study, a replication competent recombinant influenza A virus of the Í5N1 subtype expressing the H7 HA1 protein from a tri-cistronic NS segment was constructed. A heterologous dimerization domain was used to combine with the truncated NS1 protein of 73 amino acids to increase protein stability. H7 HA1, nuclear export protein coding region, and the truncated NS1 were fused in-frame into a single open reading frame via 2A self-cleaving peptides...
2018: Frontiers in Microbiology
Joon-Yong Bae, Ilseob Lee, Jin Il Kim, Sehee Park, Kirim Yoo, Miso Park, Gayeong Kim, Mee Sook Park, Joo-Yeon Lee, Chun Kang, Kisoon Kim, Man-Seong Park
Influenza B virus (IBV) is one of the human respiratory viruses and the targets of seasonal vaccination. However, the bifurcation of two antigenically distinct lineages of IBVs makes it difficult to arrange proper medical countermeasures. Moreover, compared with pathogenicity-related molecular markers known for influenza A virus, little has been known for IBVs. To understand pathogenicity caused by IBVs, we investigated the molecular determinants of IBV pathogenicity in animal models. After serial lung-to-lung passages of Victoria lineage B/Brisbane/60/2008 (Vc_BR60) and Yamagata lineage B/Wisconsin/01/2010 (Ym_WI01) viruses in BALB/c mice, we identified the mouse-adapted Vc_BR60 (maVc_BR60) and Ym_WI01 (maYm_WI01) viruses, respectively...
April 11, 2018: Journal of Virology
Hyesun Jang, Mohamed Elaish, Mahesh Kc, Michael C Abundo, Amir Ghorbani, John M Ngunjiri, Chang-Won Lee
Outbreaks of novel highly pathogenic avian influenza viruses have been reported in poultry species in the United States since 2014. These outbreaks have proven the limitations of biosecurity control programs, and new tools are needed to reinforce the current avian influenza control arsenal. Some enzootic countries have implemented inactivated influenza vaccine (IIV) in their control programs, but there are serious concerns that a long-term use of IIV without eradication may result in the selection of novel antigenically divergent strains...
2018: PloS One
Qingliang Shen, Jie Shi, Danyun Zeng, Baoyu Zhao, Pingwei Li, Wonmuk Hwang, Jae-Hyun Cho
Many intrinsically disordered proteins (IDPs) form fuzzy complexes upon binding to their targets. Although many IDPs are weakly bound in fuzzy complexes, some IDPs form high-affinity complexes. One example is the nonstructural protein 1 (NS1) of the 1918 Spanish influenza A virus, which hijacks cellular CRKII through the strong binding affinity (Kd ∼10 nM) of its proline-rich motif (PRMNS1 ) to the N-terminal Src-homology 3 domain of CRKII. However, its molecular mechanism remains elusive. Here, we examine the interplay between structural disorder of a bound PRMNS1 and its long-range electrostatic interactions...
March 27, 2018: Biophysical Journal
Sascha Trapp, Denis Soubieux, Alexandra Lidove, Evelyne Esnault, Adrien Lion, Vanaique Guillory, Alan Wacquiez, Emmanuel Kut, Pascale Quéré, Thibaut Larcher, Mireille Ledevin, Virginie Nadan, Christelle Camus-Bouclainville, Daniel Marc
BACKGROUND: Non-structural protein NS1 of influenza A viruses harbours several determinants of pathogenicity and host-range. However it is still unclear to what extent each of its two structured domains (i.e. RNA-binding domain, RBD, and effector domain, ED) contribute to its various activities. METHODS: To evaluate the respective contributions of the two domains, we genetically engineered two variants of an H7N1 low pathogenicity avian influenza virus harbouring amino-acid substitutions that impair the functionality of either domain...
March 27, 2018: Virology Journal
Jinghua Cheng, Chunling Zhang, Jie Tao, Benqiang Li, Ying Shi, Huili Liu
BACKGROUND: The influenza A virus non-structural protein 1 (NS1) is a multifunctional protein that plays an important role in virus replication, virulence and inhibition of the host antiviral immune response. In the avian influenza virus or human influenza virus, specific amino acids of NS1 have been shown to be important for the virus to antagonize host antiviral defenses and promote viral replication. However, little research has been reported regarding the swine influenza virus (SIV) NS1 protein...
March 27, 2018: Virology Journal
Milind M Thube, Pratip Shil, Rewati Kasbe, Avinash A Patil, Shailesh D Pawar, Jayati Mullick
Influenza A virus infection induces type I interferons (IFNs α/β) which activate host antiviral responses through a cascade of IFN signaling events. Herein, we compared highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses isolated from India, for their replication kinetics and ability to induce IFN-β and interferon-stimulating genes (ISGs). The H5N1 virus showed a higher replication rate and induced less IFN-β and ISGs compared to the H11N1 virus when grown in the human lung epithelial A549 cells, reflecting the generation of differential innate immune responses during infection by these viruses...
March 24, 2018: Virus Genes
Junyong Wang, Yan Zeng, Shuai Xu, Jiayun Yang, Wanbing Wang, Bo Zhong, Jinying Ge, Lei Yin, Zhigao Bu, Hong-Bing Shu, Hualan Chen, Cao-Qi Lei, Qiyun Zhu
Nonstructural protein 1 (NS1) of influenza A virus regulates innate immune responses via various mechanisms. We previously showed that a naturally occurring deletion (the EALQR motif) in the NS1 effector domain of an H5N1 swine-origin avian influenza virus impairs the inhibition of type I interferon (IFN) in chicken fibroblasts and attenuates virulence in chickens. Here, we found that the virus bearing this deletion in its NS1 effector domain showed diminished inhibition of IFN-related cytokine expression and attenuated virulence in mice...
March 21, 2018: Journal of Virology
Rei-Lin Kuo, Chi-Jene Chen, Ee-Hong Tam, Chung-Guei Huang, Li-Hsin Li, Zong-Hua Li, Pei-Chia Su, Hao-Ping Liu, Chih-Ching Wu
Influenza A virus infections can result in severe respiratory diseases. The H7N9 subtype of avian influenza A virus has been transmitted to humans and caused severe disease and death. Nonstructural protein 1 (NS1) of influenza A virus is a virulence determinant during viral infection. To elucidate the functions of the NS1 encoded by influenza A H7N9 virus (H7N9 NS1), interaction partners of H7N9 NS1 in human cells were identified with immunoprecipitation followed by SDS-PAGE coupled with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)...
March 20, 2018: Journal of Proteome Research
Klaudia Chrzastek, Dong-Hun Lee, Saad Gharaibeh, Aniko Zsak, Darrell R Kapczynski
Next-generation sequencing (NGS) technologies are a valuable tool to monitor changes in viral genomes and determine the genetic heterogeneity of viruses. In this study, NGS was applied to clinical poultry samples from Jordan to detect eleven H9N2 low pathogenic avian influenza viruses (LPAIV). All of the viruses tested belonged to Middle East A genetic group of G1 lineage. Deep sequencing demonstrated a high degree of heterogeneity of glutamine and leucine residues at position 226 in the hemagglutinin (HA) gene, which increases specificity to either avian or mammalian-type receptors...
March 7, 2018: Virology
Nathalie Lejal, Sandrine Truchet, Edna Bechor, Edwige Bouguyon, Vijay Khedkar, Nicolas Bertho, Jasmina Vidic, Pierre Adenot, Stéphanie Solier, Edgar Pick, Anny Slama-Schwok
BACKGROUND: Targeting cells of the host immune system is a promising approach to fight against Influenza A virus (IAV) infection. Macrophage cells use the NADPH oxidase-2 (NOX2) enzymatic complex as a first line of defense against pathogens by generating superoxide ions O2 - and releasing H2 O2 . Herein, we investigated whether targeting membrane -embedded NOX2 decreased IAV entry via raft domains and reduced inflammation in infected macrophages. METHODS: Confocal microscopy and western blots monitored levels of the viral nucleoprotein NP and p67phox , NOX2 activator subunit, Elisa assays quantified TNF-α levels in LPS or IAV-activated mouse or porcine alveolar macrophages pretreated with a fluorescent NOX inhibitor, called nanoshutter NS1...
March 7, 2018: Biochimica et Biophysica Acta
Chi-Ping Chan, Chun-Kit Yuen, Pak-Hin Hinson Cheung, Sin-Yee Fung, Pak-Yin Lui, Honglin Chen, Kin-Hang Kok, Dong-Yan Jin
PACT is a double-stranded RNA-binding protein that has been implicated in host-influenza A virus (IAV) interaction. PACT facilitates the action of RIG-I in the activation of the type I IFN response, which is suppressed by the viral nonstructural protein NS1. PACT is also known to interact with the IAV RNA polymerase subunit PA. Exactly how PACT exerts its antiviral activity during IAV infection remains to be elucidated. In the current study, we demonstrated the interplay between PACT and IAV polymerase. Induction of IFN-β by the IAV RNP complex was most robust when both RIG-I and PACT were expressed...
March 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Haixin Ai, Xuewei Wu, Mengyuan Qi, Li Zhang, Huan Hu, Qi Zhao, Jian Zhao, Hongsheng Liu
In recent years, new strains of influenza virus such as H7N9, H10N8, H5N6 and H5N8 had continued to emerge. There was an urgent need for discovery of new anti-influenza virus drugs as well as accurate and efficient large-scale inhibitor screening methods. In this study, we focused on six influenza virus proteins that could be anti-influenza drug targets, including neuraminidase (NA), hemagglutinin (HA), matrix protein 1 (M1), M2 proton channel (M2), nucleoprotein (NP) and non-structural protein 1 (NS1). Structure-based molecular docking was utilized to identify potential inhibitors for these drug targets from 13144 compounds in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform...
March 2, 2018: Interdisciplinary Sciences, Computational Life Sciences
Lu Guo, Yingfang Liu
NS1-binding protein (NS1-BP), which belongs to the Kelch protein superfamily, was first identified as a novel human 70 kDa protein that interacts with NS1 of Influenza A virus. It is involved in many cell functions, including pre-mRNA splicing, the ERK signalling pathway, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitylation. However, the structure of NS1-BP is still unknown, which may impede functional studies. Here, the structure of the C-terminal Kelch domain of NS1-BP (NS1-BP-C; residues 330-642) was determined at 1...
March 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
Kelei Guo, Xian Lin, Yongtao Li, Wei Qian, Zhong Zou, Huanchun Chen, Hongbo Zhou, Meilin Jin
Non-structural 1 (NS1) protein is a key virulence factor that regulates replication of influenza virus. A recombinant H5N1 virus lacking the eIF4GI-binding domain of NS1 (rNS1-SD30) exhibits significantly lower pathogenicity than H5N1 virus with an intact eIF4GI-binding domain (rNS1-wt). To further investigate this phenomenon, we performed comparative proteomics analyses to profile host proteins in chicken embryo fibroblasts (CEFs) infected with rNS1-wt and rNS1-SD30 viruses. In total, 81 differentially expressed (DE) proteins were identified at 12, 24, and 36 h post-infection...
February 2, 2018: Oncotarget
Andrés Pizzorno, Julia Dubois, Daniela Machado, Gaëlle Cartet, Aurelien Traversier, Thomas Julien, Bruno Lina, Jean-Christophe Bourdon, Manuel Rosa-Calatrava, Olivier Terrier
The interplay between influenza A viruses (IAV) and the p53 pathway has been reported in several studies, highlighting the antiviral contribution of p53. Here, we investigated the impact of IAV on the E3-ubiquitin ligase Mdm2, a major regulator of p53, and observed that IAV targets Mdm2, notably via its non-structural protein (NS1), therefore altering Mdm2 stability, p53/Mdm2 interaction and regulatory loop during the time-course of infection. This study also highlights a new antiviral facet of Mdm2 possibly increasing the list of its many p53-independent functions...
February 27, 2018: Scientific Reports
Ru Yu, Xiuli Jing, Wenjing Li, Jie Xu, Yang Xu, Liwei Geng, Changxiang Zhu, Hongmei Liu
Non-structural protein 1 (NS1) of influenza A virus is a multifunctional dimeric protein that contains a conserved N-terminal RNA binding domain. Studies have shown that NS1 suppresses RNA silencing and the NS1 proteins encoded by different influenza A virus strains exhibit differential RNA silencing suppression activities. In this study, we showed that the NS1 protein from avian influenza virus (AIV) H9N2 suppressed systemic RNA silencing induced by sense RNA or dsRNA. It resulted in more severe Potato virus X symptom, but could not reverse established systemic green fluorescent protein silencing in Nicotiana benthamiana...
February 26, 2018: Virus Genes
Hong-Su Park, GuanQun Liu, Sathya N Thulasi Raman, Shelby L Landreth, Qiang Liu, Yan Zhou
The inflammasome represents a molecular platform for the innate immune regulation and controls the pro-inflammatory cytokine production. NLRP3 inflammasome is comprised of NLRP3, ASC and pro-caspase-1. When NLRP3 inflammasome is activated, it causes ASC speck formation and caspase-1 activation, resulting in the maturation of IL-1β. NLRP3 inflammasome is regulated at multiple levels, with one level being post-translational modification. Interestingly, ubiquitination of ASC has been reported to be indispensable for the activation of NLRP3 inflammasome...
January 31, 2018: Journal of Virology
Carolin Klemm, Yvonne Boergeling, Stephan Ludwig, Christina Ehrhardt
Influenza epidemics and pandemics still represent a severe public health threat and cause significant morbidity and mortality worldwide. As intracellular parasites, influenza viruses are strongly dependent on the host cell machinery. To ensure efficient production of progeny viruses, viral proteins extensively interfere with cellular signalling pathways to inhibit antiviral responses or to activate virus-supportive functions. Here, we review various functions of the influenza virus nonstructural proteins NS1, PB1-F2, and PA-X in infected cells and how post-transcriptional modifications of these proteins affect the viral life cycle...
January 17, 2018: Trends in Microbiology
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