keyword
https://read.qxmd.com/read/38479246/cryo-em-structure-of-influenza-a-virus-ns1-and-antiviral-protein-kinase-pkr-complex
#1
JOURNAL ARTICLE
Hyeon Jin Kim, Chang Woo Han, Mi Suk Jeong, Se Bok Jang
Influenza A virus is the cause of a widespread human disease with high morbidity and mortality rates. The influenza virus encodes non-structural protein 1 (NS1), an exceedingly multifunctional virulence component. NS1 plays essential roles in viral replication and evasion of the cellular innate immune system. Protein kinase RNA-activated also known as protein kinase R (PKR) phosphorylates translation initiation factor eIF-2α on serine 51 to inhibit protein synthesis in virus-infected mammalian cells. Consequently, PKR activation inhibits mRNA translation, which results in the assert of both viral protein synthesis and cellular and possibly apoptosis in response to virus infection...
March 5, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38473897/h9n2-avian-influenza-virus-downregulates-fcry-expression-in-chicken-macrophage-cell-line-hd11-by-activating-the-jnk-mapk-pathway
#2
JOURNAL ARTICLE
Zhijian Sun, Wenjie Zhang, Jian Li, Kang Yang, Yanhao Zhang, Zili Li
The H9N2 avian influenza virus causes reduced production performance and immunosuppression in chickens. The chicken yolk sac immunoglobulins (IgY) receptor (FcRY) transports from the yolk into the embryo, providing offspring with passive immunity to infection against common poultry pathogens. FcRY is expressed in many tissues/organs of the chicken; however, there are no reports investigating FcRY expression in chicken macrophage cells, and how H9N2-infected HD11 cells (a chicken macrophage-like cell line) regulate FcRY expression remains uninvestigated...
February 24, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38473707/changes-in-the-expression-of-proteins-associated-with-neurodegeneration-in-the-brains-of-mice-after-infection-with-influenza-a-virus-with-wild-type-and-truncated-ns1
#3
JOURNAL ARTICLE
Karin Donátová, Miriam Mladá, Katarína Lopušná, Filip Baran, Tatiana Betáková
Influenza type A virus (IAV) infection is a major cause of morbidity and mortality during influenza epidemics. Recently, a specific link between IAV infection and neurodegenerative disease progression has been established. The non-structural NS1 protein of IAV regulates viral replication during infection and antagonizes host antiviral responses, contributing to influenza virulence. In the present study, we have prepared a mouse lung-to-lung adapted to the NS1-truncated virus (NS80ad). Transcriptome analysis of the gene expression in the lungs revealed that infection with wild-type A/WSN/33 (WSN), NS80, and NS80ad viruses resulted in different regulation of genes involved in signaling pathways associated with the cell proliferation, inflammatory response, and development of neurodegenerative diseases...
February 20, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38415626/the-h9n2-avian-influenza-virus-increases-apec-adhesion-to-oviduct-epithelia-by-viral-ns1-protein-mediated-activation-of-the-tgf-%C3%AE-pathway
#4
JOURNAL ARTICLE
Jinjie Han, Wenchi Chang, Junyang Fang, Xiaolan Hou, Zhijun Li, Jingyu Wang, Wen Deng
Avian influenza A (H9N2) avian influenza is a low-pathogenic avian influenza circulating in poultry and wild birds worldwide and frequently contributes to chicken salpingitis that is caused by avian pathogenic Escherichia coli (APEC), leading to huge economic losses and risks for food safety. Currently, how the H9N2 virus contributes to APEC infection and facilitates salpingitis remains elusive. In this study, in vitro chicken oviduct epithelial cell (COEC) model and in vivo studies were performed to investigate the role of H9N2 viruses on secondary APEC infection, and we identified that H9N2 virus enhances APEC infection both in vitro and in vivo ...
February 28, 2024: Journal of Virology
https://read.qxmd.com/read/38375361/antiviral-responses-versus-virus-induced-cellular-shutoff-a-game-of-thrones-between-influenza-a-virus-ns1-and-sars-cov-2-nsp1
#5
REVIEW
Ahmed Magdy Khalil, Aitor Nogales, Luis Martínez-Sobrido, Ahmed Mostafa
Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the host via hijacking essential host cell machinery components to evade the provoked antiviral innate immunity against the invading pathogen. Respiratory viral infections are usually acute with the ability to activate pattern recognition receptors (PRRs) in/on host cells, resulting in the production and release of interferons (IFNs), proinflammatory cytokines, chemokines, and IFN-stimulated genes (ISGs) to reduce virus fitness and mitigate infection...
2024: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/38328244/the-ns1-protein-of-influenza-b-virus-binds-5-triphosphorylated-dsrna-to-suppress-rig-i-activation-and-the-host-antiviral-response
#6
Ryan Woltz, Brandon Schweibenz, Susan E Tsutakawa, Chen Zhao, LiChung Ma, Ben Shurina, Gregory L Hura, Rachael John, Sergey Vorobiev, Gvt Swapna, Mihai Solotchi, John A Tainer, Robert M Krug, Smita S Patel, Gaetano T Montelione
Influenza A and B viruses overcome the host antiviral response to cause a contagious and often severe human respiratory disease. Here, integrative structural biology and biochemistry studies on non- structural protein 1 of influenza B virus (NS1B) reveal a previously unrecognized viral mechanism for innate immune evasion. Conserved basic groups of its C-terminal domain (NS1B-CTD) bind 5'- triphosphorylated double-stranded RNA (5'ppp-dsRNA), the primary pathogen-associated feature that activates the host retinoic acid-inducible gene I protein (RIG-I) to initiate interferon synthesis and the cellular antiviral response...
January 24, 2024: bioRxiv
https://read.qxmd.com/read/38257838/genomic-analyses-uncover-evolutionary-features-of-influenza-a-h3n2-viruses-in-yunnan-province-china-from-2017-to-2022
#7
JOURNAL ARTICLE
Meiling Zhang, Jienan Zhou, Ruize Ni, Xiaonan Zhao, Yaoyao Chen, Yanhong Sun, Zhaosheng Liu, Xiaoyu Han, Chunrui Luo, Xiaoqing Fu, Yong Shao
Influenza A viruses evolve at a high rate of nucleotide substitution, thereby requiring continuous monitoring to determine the efficacy of vaccines and antiviral drugs. In the current study, we performed whole-genome sequencing analyses of 253 influenza A/H3N2 strains from Yunnan Province, China, during 2017-2022. The hemagglutinin (HA) segments of Yunnan A/H3N2 strains isolated during 2017-2018 harbored a high genetic diversity due to heterogeneous distribution across branches. The mutation regularity of the predominant antigenic epitopes of HA segments in Yunnan was inconsistent in different years...
January 18, 2024: Viruses
https://read.qxmd.com/read/38223555/an-engineered-influenza-a-virus-expressing-the-co-stimulator-ox40l-as-an-oncolytic-agent-against-hepatocellular-carcinoma
#8
JOURNAL ARTICLE
Hao Yang, Guanglin Lei, Zhuoya Deng, Fang Sun, Yuying Tian, Jinxia Cheng, Hongyu Yu, Cong Li, Changqing Bai, Shaogeng Zhang, Guangwen An, Penghui Yang
BACKGROUND: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules. METHODS: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene...
2024: Journal of Hepatocellular Carcinoma
https://read.qxmd.com/read/38219420/how-the-immune-mousetrap-works-structural-evidence-for-the-immunomodulatory-action-of-a-peptide-from-influenza-ns1-protein
#9
JOURNAL ARTICLE
Yana Zabrodskaya, Vladimir Tsvetkov, Anna-Polina Shurygina, Kirill Vasyliev, Aram Shaldzhyan, Andrey Gorshkov, Alexander Kuklin, Natalya Fedorova, Vladimir Egorov
One of the critical stages of the T-cell immune response is the dimerization of the intramembrane domains of T-cell receptors (TCR). Structural similarities between the immunosuppressive domains of viral proteins and the transmembrane domains of TCR have led several authors to hypothesize the mechanism of immune response suppression by highly pathogenic viruses: viral proteins embed themselves in the membrane and act on the intramembrane domain of the TCRalpha subunit, hindering its functional oligomerization...
January 9, 2024: Biophysical Chemistry
https://read.qxmd.com/read/38166085/role-of-influenza-a-virus-protein-ns1-in-regulating-host-nuclear-body-nd10-complex-formation-and-its-involvement-in-establishment-of-viral-pathogenesis
#10
JOURNAL ARTICLE
Ujjal Das, Mamta Chawla-Sarkar, Swati Roy Gangopadhyay, Sanjit Dey, Rakhi Dey Sharma
Influenza viral infection is a seasonal infection which causes widespread acute respiratory issues among humans globally. This virus changes its surface receptor composition to escape the recognition process by the host's immune cells. Therefore, the present study focussed to identify some other important viral proteins which have a significant role in establishment of infection and having apparent conserved structural composition. This could facilitate the permanent vaccine development process or help in designing a drug against IAV (influenza A virus) infection which will eliminate the seasonal flu shot vaccination process...
2024: PloS One
https://read.qxmd.com/read/38156568/determination-of-cold-adapted-influenza-virus-orthomyxoviridae-alphainfluenzavirus-polymerase-activity-by-the-minigenome-method-with-a-fluorescent-protein
#11
JOURNAL ARTICLE
P A Ivanov, A V Lyashko, V Y Kost, N F Lomakina, A A Rtishchev, N I Bunkova, T A Timofeeva, M A Balanova, S A Ionov, D V Gorikov, S G Markushin
INTRODUCTION: Polymerase proteins PB1 and PB2 determine the cold-adapted phenotype of the influenza virus A/Krasnodar/101/35/59 (H2N2), as was shown earlier. OBJECTIVE: The development of the reporter construct to determine the activity of viral polymerase at 33 and 37 °C using the minigenome method. MATERIALS AND METHODS: Co-transfection of Cos-1 cells with pHW2000 plasmids expressing viral polymerase proteins PB1, PB2, PA, NP (minigenome) and reporter construct...
December 26, 2023: Voprosy Virusologii
https://read.qxmd.com/read/38152399/roles-and-functions-of-iav-proteins-in-host-immune-evasion
#12
REVIEW
Farooq Rashid, Zhixun Xie, Meng Li, Zhiqin Xie, Sisi Luo, Liji Xie
Influenza A viruses (IAVs) evade the immune system of the host by several regulatory mechanisms. Their genomes consist of eight single-stranded segments, including nonstructural proteins (NS), basic polymerase 1 (PB1), basic polymerase 2 (PB2), hemagglutinin (HA), acidic polymerase (PA), matrix (M), neuraminidase (NA), and nucleoprotein (NP). Some of these proteins are known to suppress host immune responses. In this review, we discuss the roles, functions and underlying strategies adopted by IAV proteins to escape the host immune system by targeting different proteins in the interferon (IFN) signaling pathway, such as tripartite motif containing 25 (TRIM25), inhibitor of nuclear factor κB kinase (IKK), mitochondrial antiviral signaling protein (MAVS), Janus kinase 1 (JAK1), type I interferon receptor (IFNAR1), interferon regulatory factor 3 (IRF3), IRF7, and nuclear factor-κB (NF-κB)...
2023: Frontiers in Immunology
https://read.qxmd.com/read/38140686/generation-and-characterization-of-an-influenza-d-reporter-virus
#13
JOURNAL ARTICLE
Lukas Probst, Laura Laloli, Manon Flore Licheri, Matthias Licheri, Mitra Gultom, Melle Holwerda, Philip V'kovski, Ronald Dijkman
Influenza D virus (IDV) can infect various livestock animals, such as cattle, swine, and small ruminants, and was shown to have zoonotic potential. Therefore, it is important to identify viral factors involved in the broad host tropism and identify potential antiviral compounds that can inhibit IDV infection. Recombinant reporter viruses provide powerful tools for studying viral infections and antiviral drug discovery. Here we present the generation of a fluorescent reporter IDV using our previously established reverse genetic system for IDV...
December 16, 2023: Viruses
https://read.qxmd.com/read/38076881/n-terminal-acetylation-of-the-influenza-ribonuclease-pa-x-promotes-nuclear-localization-and-host-shutoff-activity-in-a-multifaceted-manner
#14
Raecliffe E Daly, Idalia Myasnikov, Marta Maria Gaglia
To counteract host antiviral responses, influenza A virus triggers a global reduction of cellular gene expression, a process termed "host shutoff." A key effector of influenza A virus host shutoff is the viral endoribonuclease PA-X, which degrades host mRNAs. While many of the molecular determinants of PA-X activity remain unknown, a previous study identified a requirement for N-terminal acetylation of PA-X for its host shutoff activity, but did not address how this modification promotes activity. Here, we report that PA-X N-terminal acetylation has two functions that can be separated based on the position of the acetylation, on the first amino acid, i...
December 2, 2023: bioRxiv
https://read.qxmd.com/read/38062753/effects-of-the-ns1-nolc1-protein-interaction-on-rrna-synthesis-through-trf2-regulation-under-nucleolar-stress
#15
JOURNAL ARTICLE
Man Zhang, Yingyue Zeng, Fengchao Wang, Huawei Feng, Qingqing Liu, Feng Li, Shan Zhao, Jian Zhao, Zhikui Liu, Fangliang Zheng, Hongsheng Liu
To investigate the effects and underlying molecular mechanisms of the interaction between nonstructural protein (NS1) and nucleolar and coiled-body phosphoprotein 1 (NOLC1) on rRNA synthesis via nucleolar telomeric repeat-binding factor 2 (TRF2) under nucleolar stress in avian influenza A virus infection. The analysis of TRF2 ties into the exploration of ribosomal protein L11 (RPL11) and mouse double minute 2 (MDM2) because TRF2 has been found to interact with NOLC1, and the RPL11-MDM2 pathway plays an important role in nucleolar regulation and cellular processes...
December 7, 2023: AIDS Research and Human Retroviruses
https://read.qxmd.com/read/38038453/the-er-golgi-transport-of-influenza-virus-through-ns1-sec13-association-during-virus-replication
#16
JOURNAL ARTICLE
Sonja C J H Chua, Jianzhou Cui, Karishma Sachaphibulkij, Isabelle Siang Ling Tan, Hui Qing Tan, Hong Meng Lim, David Engelberg, Lina H K Lim
Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. Endoplasmic reticulum-to-Golgi transport is an important pathway of influenza virus replication and viral export...
December 1, 2023: Microbiology Spectrum
https://read.qxmd.com/read/37951883/development-of-a-robust-taqman-probe-based-one-step-multiplex-rt-qpcr-for-simultaneous-detection-of-sars-cov-2-and-influenza-a-b-viruses
#17
JOURNAL ARTICLE
Hamidreza Abbasi, Hadi Razavi Nikoo, Fatemeh Fotouhi, Ayyoob Khosravi
BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Influenza A, and Influenza B viruses is essential for rapid differential diagnosis in patients with similar symptoms, especially during "flu season" in the post-pandemic era. So far, several multiplex methods have been approved for the simultaneous detection of SARS-CoV-2, Influenza A, and Influenza B. However, due to the rapid mutation rate of the SARS-CoV-2 genome and the emergence of new variants, existing methods must be improved and updated...
November 11, 2023: BMC Microbiology
https://read.qxmd.com/read/37896883/diversity-and-complexity-of-internally-deleted-viral-genomes-in-influenza-a-virus-subpopulations-with-enhanced-interferon-inducing-phenotypes
#18
JOURNAL ARTICLE
Amir Ghorbani, John M Ngunjiri, Gloria Rendon, Christopher B Brooke, Scott P Kenney, Chang-Won Lee
Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therapeutic and immunogenic applications. In this study, we aimed to investigate the diversity and complexity of the internally deleted IAV genomes within a panel of plaque-purified avian influenza viruses selected for their enhanced interferon-inducing phenotypes...
October 17, 2023: Viruses
https://read.qxmd.com/read/37896840/structural-investigations-of-interactions-between-the-influenza-a-virus-ns1-and-host-cellular-proteins
#19
REVIEW
Morgan E Blake, Alex B Kleinpeter, Alexander S Jureka, Chad M Petit
The Influenza A virus is a continuous threat to public health that causes yearly epidemics with the ever-present threat of the virus becoming the next pandemic. Due to increasing levels of resistance, several of our previously used antivirals have been rendered useless. There is a strong need for new antivirals that are less likely to be susceptible to mutations. One strategy to achieve this goal is structure-based drug development. By understanding the minute details of protein structure, we can develop antivirals that target the most conserved, crucial regions to yield the highest chances of long-lasting success...
October 7, 2023: Viruses
https://read.qxmd.com/read/37876781/modulation-of-influenza-a-virus-ns1-expression-reveals-prioritization-of-host-response-antagonism-at-single-cell-resolution
#20
JOURNAL ARTICLE
Qing Yang, Anna E Elz, Maryline Panis, Ting Liu, Benjamin E Nilsson-Payant, Daniel Blanco-Melo
Influenza A virus (IAV) is an important human respiratory pathogen that causes significant seasonal epidemics and potential devastating pandemics. As part of its life cycle, IAV encodes the multifunctional protein NS1, that, among many roles, prevents immune detection and limits interferon (IFN) production. As distinct host immune pathways exert different selective pressures against IAV, as replication progresses, we expect a prioritization in the host immune antagonism by NS1. In this work, we profiled bulk transcriptomic differences in a primary bronchial epithelial cell model facing IAV infections at distinct NS1 levels...
2023: Frontiers in Microbiology
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