scholarly journals Influenza Virus Down-Modulates G6PD Expression and Activity to Induce Oxidative Stress and Promote Its Replication

2022 ◽  
Vol 11 ◽  
Author(s):  
Marta De Angelis ◽  
Donatella Amatore ◽  
Paola Checconi ◽  
Alessandra Zevini ◽  
Alessandra Fraternale ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Virus Replication ◽  
Influenza Virus Infection ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Host Cells ◽  
Related Factor ◽  
Expression And Activity

Influenza virus infection induces oxidative stress in host cells by decreasing the intracellular content of glutathione (GSH) and increasing reactive oxygen species (ROS) level. Glucose-6-phosphate dehydrogenase (G6PD) is responsible for the production of reducing equivalents of nicotinamide adenine dinucleotide phosphate (NADPH) that is used to regenerate the reduced form of GSH, thus restoring redox homeostasis. Cells deficient in G6PD display elevated levels of ROS and an increased susceptibility to viral infection, although the consequences of G6PD modulation during viral infection remain to be elucidated. In this study, we demonstrated that influenza virus infection decreases G6PD expression and activity, resulting in an increase in oxidative stress and virus replication. Moreover, the down regulation of G6PD correlated with a decrease in the expression of nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor that regulates the expression of the antioxidant response gene network. Also down-regulated in influenza virus infected cells was sirtuin 2 (SIRT2), a NADPH-dependent deacetylase involved in the regulation of G6PD activity. Acetylation of G6PD increased during influenza virus infection in a manner that was strictly dependent on SIRT2 expression. Furthermore, the use of a pharmacological activator of SIRT2 rescued GSH production and NRF2 expression, leading to decreased influenza virus replication. Overall, these data identify a novel strategy used by influenza virus to induce oxidative stress and to favor its replication in host cells. These observations furthermore suggest that manipulation of metabolic and oxidative stress pathways could define new therapeutic strategies to interfere with influenza virus infection.

scholarly journals Brugada-Like Electrocardiographic Changes during Influenza Infection

2003 ◽  
Vol 31 (3) ◽  
pp. 244-246 ◽  
Author(s):  
K Kusaka ◽  
J Yamakawa ◽  
K Kawaura ◽  
T Itoh ◽  
T Takahashi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Brugada Syndrome ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Ecg Changes ◽  
Early Repolarization ◽  
Electrocardiographic Changes

We describe a 32-year-old man with electrocardiographic (ECG) changes consistent with Brugada syndrome and influenza virus infection. The ECG pattern changed after 1 week to one of early repolarization in V1 and V2. This case suggests an association between Brugada syndrome and viral infection.

The role of oxidative stress in influenza virus infection

2017 ◽  
Vol 19 (12) ◽  
pp. 580-586 ◽  
Author(s):  
Miaomiao Liu ◽  
Fangzhao Chen ◽  
Teng Liu ◽  
Feimin Chen ◽  
Shuwen Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection

scholarly journals Metabolomic Analysis of Influenza A Virus A/WSN/1933 (H1N1) Infected A549 Cells during First Cycle of Viral Replication

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1007 ◽  
Author(s):  
Xiaodong Tian ◽  
Kun Zhang ◽  
Jie Min ◽  
Can Chen ◽  
Ying Cao ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cell Metabolism ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Tca Cycle ◽  
Host Cells ◽  
Pathway Analyses

Influenza A virus (IAV) has developed strategies to utilize host metabolites which, after identification and isolation, can be used to discover the value of immunometabolism. During this study, to mimic the metabolic processes of influenza virus infection in human cells, we infect A549 cells with H1N1 (WSN) influenza virus and explore the metabolites with altered levels during the first cycle of influenza virus infection using ultra-high-pressure liquid chromatography–quadrupole time-of-flight mass spectrometer (UHPLC–Q-TOF MS) technology. We annotate the metabolites using MetaboAnalyst and the Kyoto Encyclopedia of Genes and Genomes pathway analyses, which reveal that IAV regulates the abundance of the metabolic products of host cells during early infection to provide the energy and metabolites required to efficiently complete its own life cycle. These metabolites are correlated with the tricarboxylic acid (TCA) cycle and mainly are involved in purine, lipid, and glutathione metabolisms. Concurrently, the metabolites interact with signal receptors in A549 cells to participate in cellular energy metabolism signaling pathways. Metabonomic analyses have revealed that, in the first cycle, the virus not only hijacks cell metabolism for its own replication, but also affects innate immunity, indicating a need for further study of the complex relationship between IAV and host cells.

scholarly journals Mitochondrial morphodynamics alteration induced by influenza virus infection as a new antiviral strategy

2021 ◽  
Vol 17 (2) ◽  
pp. e1009340
Author(s):  
Irene Pila-Castellanos ◽  
Diana Molino ◽  
Joe McKellar ◽  
Laetitia Lines ◽  
Juliane Da Graca ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endoplasmic Reticulum ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Host Cells ◽  
Virus Infections ◽  
Contact Sites ◽  
Virus Trafficking ◽  
Influenza Viral Infection

Influenza virus infections are major public health threats due to their high rates of morbidity and mortality. Upon influenza virus entry, host cells experience modifications of endomembranes, including those used for virus trafficking and replication. Here we report that influenza virus infection modifies mitochondrial morphodynamics by promoting mitochondria elongation and altering endoplasmic reticulum-mitochondria tethering in host cells. Expression of the viral RNA recapitulates these modifications inside cells. Virus induced mitochondria hyper-elongation was promoted by fission associated protein DRP1 relocalization to the cytosol, enhancing a pro-fusion status. We show that altering mitochondrial hyper-fusion with Mito-C, a novel pro-fission compound, not only restores mitochondrial morphodynamics and endoplasmic reticulum-mitochondria contact sites but also dramatically reduces influenza replication. Finally, we demonstrate that the observed Mito-C antiviral property is directly connected with the innate immunity signaling RIG-I complex at mitochondria. Our data highlight the importance of a functional interchange between mitochondrial morphodynamics and innate immunity machineries in the context of influenza viral infection.

scholarly journals Glycomic analysis of host response reveals high mannose as a key mediator of influenza severity

2020 ◽  
Vol 117 (43) ◽  
pp. 26926-26935
Author(s):  
Daniel W. Heindel ◽  
Sujeethraj Koppolu ◽  
Yue Zhang ◽  
Brian Kasper ◽  
Lawrence Meche ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Influenza Virus Infection ◽  
Host Cells ◽  
Severe Illness ◽  
Dependent Manner ◽  
High Mannose ◽  
The Impact

Influenza virus infections cause a wide variety of outcomes, from mild disease to 3 to 5 million cases of severe illness and ∼290,000 to 645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose-dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity.

scholarly journals Extreme heterogeneity of influenza virus infection in single cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Alistair B Russell ◽  
Cole Trapnell ◽  
Jesse D Bloom
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Single Cells ◽  
Influenza Virus Infection ◽  
Viral Gene ◽  
Viral Mrnas ◽  
Cellular Genes ◽  
Infected Cells ◽  
Cell Variation

Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

scholarly journals Modelling within-host macrophage dynamics in influenza virus infection

2020 ◽  
Author(s):  
Ke Li ◽  
James M. McCaw ◽  
Pengxing Cao
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Dynamic Model ◽  
Macrophage Activation ◽  
Negative Relationship ◽  
Influenza Virus Infection ◽  
Health Concern ◽  
Viral Shedding ◽  
Excessive Accumulation

AbstractHuman respiratory disease associated with influenza virus infection is of significant public health concern. Macrophages, as part of the front line of host innate cellular defence, have been shown to play an important role in controlling viral replication. However, fatal outcomes of infection, as evidenced in patients infected with highly pathogenic viral strains, are often associated with prompt activation and excessive accumulation of macrophages. Activated macrophages can produce a large amount of pro-inflammatory cytokines, which leads to severe symptoms and at times death. However, the mechanism for rapid activation and excessive accumulation of macrophages during infection remains unclear. It has been suggested that the phenomena may arise from complex interactions between macrophages and influenza virus. In this work, we develop a novel mathematical model to study the relationship between the level of macrophage activation and the level of viral shedding in influenza virus infection. Our model combines a dynamic model of viral infection, a dynamic model of macrophages and the essential interactions between the virus and macrophages. Our model predicts that the level of macrophage activation can be negatively correlated with the level of viral shedding when viral infectivity is sufficiently high. We further identify that temporary depletion of resting macrophages in response to viral infection is a major driver in our model for the negative relationship between macrophage activation and viral shedding, providing new insight into the mechanisms that regulate macrophage activation. Our model serves as a framework to study the complex dynamics of virus-macrophage interactions and provides a mechanistic explanation for existing experimental observations, contributing to an enhanced understanding of the role of macrophages in influenza viral infection.

scholarly journals Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

2010 ◽  
Vol 84 (22) ◽  
pp. 12058-12068 ◽  
Author(s):  
Joseph N. Brown ◽  
Robert E. Palermo ◽  
Carole R. Baskin ◽  
Marina Gritsenko ◽  
Patrick J. Sabourin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
Viral Infection ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Virus Infection ◽  
Delayed Response ◽  
Protein Database ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza

ABSTRACT The host proteome response and molecular mechanisms that drive disease in vivo during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (Macaca fascicularis) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a “core” response to viral infection from a “high” response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process.

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