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 IFN-λ: A new spotlight in innate immunity against influenza virus infection

2018 ◽  
Vol 9 (10) ◽  
pp. 832-837 ◽  
Author(s):  
Yeping Sun ◽  
Jingwen Jiang ◽  
Po Tien ◽  
Wenjun Liu ◽  
Jing Li
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection

scholarly journals Protection against Influenza Virus Infection of Mice Fed Bifidobacterium breve YIT4064

1999 ◽  
Vol 6 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Hisako Yasui ◽  
Junko Kiyoshima ◽  
Tetuji Hori ◽  
Kan Shida
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Oral Administration ◽  
Lower Respiratory Tract ◽  
Influenza Virus Infection ◽  
Oral Immunization ◽  
Igg Antibodies ◽  
Virus Infections ◽  
Bifidobacterium Breve ◽  
Specific Igg

ABSTRACT Mice fed Bifidobacterium breve YIT4064 and immunized orally with influenza virus were more strongly protected against influenza virus infection of the lower respiratory tract than ones immunized with influenza virus only. The number of mice with enhanced anti-influenza virus immunoglobulin G (IgG) in serum upon oral administration of B. breve YIT4064 and oral immunization with influenza virus was significantly greater than that upon oral immunization with influenza virus only. These findings demonstrated that the oral administration of B. breve YIT4064 increased anti-influenza virus IgG antibodies in serum and protected against influenza virus infection. The oral administration of B. breve YIT4064 may enhance antigen-specific IgG against various pathogenic antigens taken orally and induce protection against various virus infections.

Respiratory epithelial cells in innate immunity to influenza virus infection

2010 ◽  
Vol 343 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Catherine J. Sanders ◽  
Peter C. Doherty ◽  
Paul G. Thomas
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial

The fate of resident alveolar macrophages upon influenza virus infection is the result of a complex crosstalk among different innate immunity cell populations

2018 ◽  
Author(s):  
C Malainou ◽  
B Selvakumar ◽  
C Peteranderl ◽  
W Seeger ◽  
J Lohmeyer ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Virus Infection ◽  
Alveolar Macrophages ◽  
Influenza Virus Infection ◽  
Cell Populations

scholarly journals Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 434 ◽  
Author(s):  
Christopher E. Lopez ◽  
Kevin L. Legge
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Virus Infections ◽  
Universal Vaccine

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural 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 Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies

2015 ◽  
Vol 11 (8) ◽  
pp. e1004334 ◽  
Author(s):  
Pengxing Cao ◽  
Ada W. C. Yan ◽  
Jane M. Heffernan ◽  
Stephen Petrie ◽  
Robert G. Moss ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Exposure Interval

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 Influenza Virus Evades Innate and Adaptive Immunity via the NS1 Protein

2006 ◽  
Vol 80 (13) ◽  
pp. 6295-6304 ◽  
Author(s):  
Ana Fernandez-Sesma ◽  
Svetlana Marukian ◽  
Barbara J. Ebersole ◽  
Dorothy Kaminski ◽  
Man-Seong Park ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Virus Infection ◽  
Adaptive Immunity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Type I ◽  
Ns1 Protein ◽  
Dc Maturation

ABSTRACT Both antibodies and T cells contribute to immunity against influenza virus infection. However, the generation of strong Th1 immunity is crucial for viral clearance. Interestingly, we found that human dendritic cells (DCs) infected with influenza A virus have lower allospecific Th1-cell stimulatory abilities than DCs activated by other stimuli, such as lipopolysaccharide and Newcastle disease virus infection. This weak stimulatory activity correlates with a suboptimal maturation of the DCs following infection with influenza A virus. We next investigated whether the influenza A virus NS1 protein could be responsible for the low levels of DC maturation after influenza virus infection. The NS1 protein is an important virulence factor associated with the suppression of innate immunity via the inhibition of type I interferon (IFN) production in infected cells. Using recombinant influenza and Newcastle disease viruses, with or without the NS1 gene from influenza virus, we found that the induction of a genetic program underlying DC maturation, migration, and T-cell stimulatory activity is specifically suppressed by the expression of the NS1 protein. Among the genes affected by NS1 are those coding for macrophage inflammatory protein 1β, interleukin-12 p35 (IL-12 p35), IL-23 p19, RANTES, IL-8, IFN-α/β, and CCR7. These results indicate that the influenza A virus NS1 protein is a bifunctional viral immunosuppressor which inhibits innate immunity by preventing type I IFN release and inhibits adaptive immunity by attenuating human DC maturation and the capacity of DCs to induce T-cell responses. Our observations also support the potential use of NS1 mutant influenza viruses as live attenuated influenza virus vaccines.

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