Role of the Innate Cytokine Storm Induced by the Influenza A Virus

2019 ◽  
Vol 32 (6) ◽  
pp. 244-251 ◽  
Author(s):  
Yinuo Gu ◽  
Alan Chen-Yu Hsu ◽  
Zhiqiang Pang ◽  
He Pan ◽  
Xu Zuo ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Cytokine Storm

scholarly journals The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus

2021 ◽  
Vol 22 (5) ◽  
pp. 2409
Author(s):  
Anastasia A. Bizyaeva ◽  
Dmitry A. Bunin ◽  
Valeria L. Moiseenko ◽  
Alexandra S. Gambaryan ◽  
Sonja Balk ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Core Structure ◽  
Dna Aptamer ◽  
Tertiary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Flanking Sequences ◽  
Related Proteins

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.

MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation

2016 ◽  
Vol 8 (17) ◽  
pp. 2017-2031 ◽  
Author(s):  
Simona Panella ◽  
Maria Elena Marcocci ◽  
Ignacio Celestino ◽  
Sergio Valente ◽  
Clemens Zwergel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Influenza A Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Lung Epithelial Cells ◽  
Lung Epithelial

The role of host cell Rab GTPases in influenza A virus infections

2021 ◽  
Author(s):  
Jing Wu ◽  
Jiaqi Gu ◽  
Li Shen ◽  
Xiaonan Jia ◽  
Yiqian Yin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Respiratory Infections ◽  
Small Gtpase ◽  
Regulatory Mechanisms ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Virus Infections ◽  
Adaptation Mechanisms

Influenza A virus (IAV) is a crucial cause of respiratory infections in humans worldwide. Therefore, studies should clarify adaptation mechanisms of IAV and critical factors of the viral pathogenesis in human hosts. GTPases of the Rab family are the largest branch of the Ras-like small GTPase superfamily, and they regulate almost every step during vesicle-mediated trafficking. Evidence has shown that Rab proteins participate in the lifecycle of IAV. In this mini-review, we outline the regulatory mechanisms of different Rab proteins in the lifecycle of IAV. Understanding the role of Rab proteins in IAV infections is important to develop broad-spectrum host-targeted antiviral strategies.

Role of the chaperone protein 14-3-3ε in the regulation of influenza A virus-activated beta interferon

2021 ◽  
Author(s):  
Ee-Hong Tam ◽  
Yen-Chin Liu ◽  
Chian-Huey Woung ◽  
Helene Minyi Liu ◽  
Guan-Hong Wu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Ns1 Protein ◽  
Chaperone Protein ◽  
Influenza A Virus Infection

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in RIG-I translocation to MAVS to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49 th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C-terminus-truncated NS1 with T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in RIG-I translocation that induces type I IFN expression, and that NS1 protein prevents RIG-I translocation to mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

scholarly journals Molecular Events Involved in Influenza A Virus-Induced Cell Death

2022 ◽  
Vol 12 ◽  
Author(s):  
Rui Gui ◽  
Quanjiao Chen
Keyword(s):  
Cell Death ◽  
Influenza A Virus ◽  
Influenza A ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Tissue Destruction ◽  
Inflammatory Reactions ◽  
Molecular Events ◽  
Host Death

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death. Thus, the struggle between the host and virus determines whether the host survives. Influenza A virus (IAV) infection in humans can lead to unbridled hyper-inflammatory reactions and cause serious illnesses and even death. A full understanding of the molecular mechanisms and regulatory networks through which IAVs induce cell death could facilitate the development of more effective antiviral treatments. In this review, we discuss current progress in research on cell death induced by IAV infection and evaluate the role of cell death in IAV replication and disease prognosis.

Characterization of proteins with Siaα2-3/6Gal-linked glycans from bovine milk and role of their glycans against influenza A virus

2018 ◽  
Vol 9 (10) ◽  
pp. 5198-5208 ◽  
Author(s):  
Hanjie Yu ◽  
Yaogang Zhong ◽  
Zhiwei Zhang ◽  
Xiawei Liu ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Bovine Milk ◽  
Milk Proteins ◽  
Biological Functions ◽  
Wide Range ◽  
Range Of Functions ◽  
Bovine Milk Proteins

The bovine milk proteins have a wide range of functions, but the role of the attached glycans in their biological functions has not been fully understood yet.

scholarly journals Pathogenesis of COVID-19-induced ARDS: implications for an ageing population

2020 ◽  
Vol 56 (3) ◽  
pp. 2002049 ◽  
Author(s):  
Manuel A. Torres Acosta ◽  
Benjamin D. Singer
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Distress Syndrome ◽  
Clinical Presentation ◽  
Vascular Endothelial Cells ◽  
Interferon Γ ◽  
Advanced Age ◽  
Ageing Population ◽  
Vascular Endothelial

The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.

scholarly journals The Zα2 domain of ZBP1 is a molecular switch regulating influenza-induced PANoptosis and perinatal lethality during development

2020 ◽  
Vol 295 (24) ◽  
pp. 8325-8330 ◽  
Author(s):  
Sannula Kesavardhana ◽  
R. K. Subbarao Malireddi ◽  
Amanda R. Burton ◽  
Shaina N. Porter ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Cell Death ◽  
Nucleic Acids ◽  
Influenza A Virus ◽  
Nlrp3 Inflammasome ◽  
Influenza A ◽  
Defense Responses ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Perinatal Lethality

Z-DNA-binding protein 1 (ZBP1) is an innate immune sensor of nucleic acids that regulates host defense responses and development. ZBP1 activation triggers inflammation and pyroptosis, necroptosis, and apoptosis (PANoptosis) by activating receptor-interacting Ser/Thr kinase 3 (RIPK3), caspase-8, and the NLRP3 inflammasome. ZBP1 is unique among innate immune sensors because of its N-terminal Zα1 and Zα2 domains, which bind to nucleic acids in the Z-conformation. However, the specific role of these Zα domains in orchestrating ZBP1 activation and subsequent inflammation and cell death is not clear. Here we generated Zbp1ΔZα2/ΔZα2 mice that express ZBP1 lacking the Zα2 domain and demonstrate that this domain is critical for influenza A virus–induced PANoptosis and underlies perinatal lethality in mice in which the RIP homotypic interaction motif domain of RIPK1 has been mutated (Ripk1mRHIM/mRHIM). Deletion of the Zα2 domain in ZBP1 abolished influenza A virus–induced PANoptosis and NLRP3 inflammasome activation. Furthermore, deletion of the Zα2 domain of ZBP1 was sufficient to rescue Ripk1mRHIM/mRHIM mice from perinatal lethality caused by ZBP1-driven cell death and inflammation. Our findings identify the essential role of the Zα2 domain of ZBP1 in several physiological functions and establish a link between Z-RNA sensing via the Zα2 domain and promotion of influenza-induced PANoptosis and perinatal lethality.

scholarly journals Role of Autophagy and Apoptosis in the Postinfluenza Bacterial Pneumonia

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Qin ◽  
Yuan Yang ◽  
Hongren Wang ◽  
Jun Luo ◽  
Xiaojun Huang ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Influenza A Virus ◽  
Bacterial Pneumonia ◽  
Influenza A ◽  
Bacterial Infections ◽  
Research Progress ◽  
The Past ◽  
Recent Research Progress ◽  
Increased Susceptibility

The risk of influenza A virus (IAV) is more likely caused by secondary bacterial infections. During the past decades, a great amount of studies have been conducted on increased morbidity from secondary bacterial infections following influenza and provide an increasing number of explanations for the mechanisms underlying the infections. In this paper, we first review the recent research progress that IAV infection increased susceptibility to bacterial infection. We then propose an assumption that autophagy and apoptosis manipulation are beneficial to antagonize post-IAV bacterial infection and discuss the clinical significance.

Sign in / Sign up

Export Citation Format

Share Document