Foot-and-mouth disease virus infection stimulates innate immune signaling in the mouse macrophage RAW 264.7 cells

2018 ◽  
Vol 64 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Xiaoying Zhi ◽  
Jianliang Lv ◽  
Yanquan Wei ◽  
Ping Du ◽  
Yanyan Chang ◽  
...  
Keyword(s):  
Immune Response ◽  
Foot And Mouth Disease ◽  
Innate Immune ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Mouse Macrophage ◽  
Fmdv Infection ◽  
Serotype O ◽  
Fmdv Serotype ◽  
Mouth Disease Virus

The innate immune system acts as the first line of defense against invasion by bacterial and viral pathogens. The role of macrophages in innate immune responses to foot-and-mouth disease virus (FMDV) is poorly understood. To determine the mechanism underlying activation of innate immunity after FMDV infection in macrophages, we performed FMDV infection in mouse macrophage RAW 264.7 cells and found that FMDV serotype O infection induced a cytopathic effect. We then evaluated the gene expression profile in macrophage RAW 264.7 cells after FMDV infection using systematic microarray analysis. Gene ontology annotation and enrichment analysis revealed that FMDV promoted expression in a group of genes that are enriched in innate immune response and inflammatory response processes. Further research demonstrated that FMDV serotype O infection enhanced NF-κB, Toll-like, and RIG-I-like receptor signaling pathways and proteins expression and increased transcription and expression of a series of cytokines and interferons, as proved by qRT-PCR, Western blot, ELISA, and dual-luciferase reporter assay. Our study concluded that FMDV infection triggers the innate immune response in macrophages after activation of multiple innate immune pathway receptors and proteins by FMDV serotype O, resulting in activation and secretion of a series of cytokines and interferons.

scholarly journals Foot-and-Mouth Disease Virus Evades Innate Immune Response by 3C-Targeting of MDA5

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 271
Author(s):  
Hyejin Kim ◽  
Ah-Young Kim ◽  
Jieun Choi ◽  
Sun Young Park ◽  
Sang Hyun Park ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Expression ◽  
Innate Immune Response ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Type I ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease (FMD) is a highly contagious disease caused by FMD virus (FMDV) in cloven-hoofed animals. Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are representative receptors in the cytoplasm for the detection of viral RNA and trigger antiviral responses, leading to the production of type I interferon. Although MDA5 is a crucial receptor for sensing picornavirus RNA, the interplay between MDA5 and FMDV is relatively unknown compared to the interplay between RIG-I and FMDV. Here, we observed that the FMDV infection inhibits MDA5 protein expression. Of the non-structural proteins, the Lb and 3C proteinases (Lbpro and 3Cpro) were identified to be primarily responsible for this inhibition. However, the inhibition by 3Cpro was independent of proteasome, lysosome and caspase-dependent pathway and was by 3C protease activity. A direct interaction between 3Cpro and MDA5 protein was observed. In conclusion, this is the first report that 3Cpro inhibits MDA5 protein expression as a mechanism to evade the innate immune response during FMDV infection. These results elucidate the pathogenesis of FMDV and provide fundamental insights for the development of a novel vaccine or therapeutic agent.

scholarly journals Synthetic RNAs Mimicking Structural Domains in the Foot-and-Mouth Disease Virus Genome Elicit a Broad Innate Immune Response in Porcine Cells Triggered by RIG-I and TLR Activation

Viruses ◽  
2015 ◽  
Vol 7 (7) ◽  
pp. 3954-3973 ◽  
Author(s):  
Belén Borrego ◽  
Miguel Rodríguez-Pulido ◽  
Concepción Revilla ◽  
Belén Álvarez ◽  
Francisco Sobrino ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Virus ◽  
Innate Immune Response ◽  
Foot And Mouth Disease ◽  
Virus Genome ◽  
Mouth Disease ◽  
Innate Immune ◽  
Structural Domains ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Staphylococcus aureus Biofilm-Conditioned Medium Impairs Macrophage-Mediated Antibiofilm Immune Response by Upregulating KLF2 Expression

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Talib Alboslemy ◽  
Bing Yu ◽  
Tara Rogers ◽  
Min-Ho Kim
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Conditioned Medium ◽  
Innate Immune Response ◽  
Immune Defense ◽  
Innate Immune ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Content Type ◽  
Cell Functions

ABSTRACT Staphylococcus aureus infections associated with the formation of biofilms on medical implants or host tissue play a critical role in the persistence of chronic infections. One critical mechanism of biofilm infection that leads to persistent infection lies in the capacity of biofilms to evade the macrophage-mediated innate immune response. It is now increasingly apparent that microorganisms exploit the negative regulatory mechanisms of the pattern recognition receptor (PRR)-mediated inflammatory response to subvert host cell functions by using various virulence factors. However, the detailed molecular mechanism, along with the identity of a target molecule, underlying the evasion of the macrophage-mediated innate immune response against S. aureus infection associated with biofilm formation remains to be elucidated. Here, using an in vitro culture model of murine macrophage-like RAW 264.7 cells, we demonstrate that S. aureus biofilm-conditioned medium significantly attenuated the capacity for macrophage bactericidal and proinflammatory responses. Importantly, the responses were associated with attenuated activation of NF-κB and increased expression of Kruppel-like factor 2 (KLF2) in RAW 264.7 cells. Small interfering RNA (siRNA)-mediated silencing of KLF2 in RAW 264.7 cells could restore the activation of NF-κB toward the bactericidal activity and generation of proinflammatory cytokines in the presence of S. aureus biofilm-conditioned medium. Collectively, our results suggest that factors secreted from S. aureus biofilms might exploit the KLF2-dependent negative regulatory mechanism to subvert macrophage-mediated innate immune defense against S. aureus biofilms.

Development of foot-and-mouth disease virus (FMDV) serotype O virus-like-particles (VLPs) vaccine and evaluation of its potency

2012 ◽  
Vol 96 (3) ◽  
pp. 288-295 ◽  
Author(s):  
B. Mohana Subramanian ◽  
M. Madhanmohan ◽  
Rajan Sriraman ◽  
R.V. Chandrasekhar Reddy ◽  
S. Yuvaraj ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Virus Like Particles ◽  
Serotype O ◽  
Fmdv Serotype ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Implication of Broadly Neutralizing Bovine Monoclonal Antibodies in the Development of an Enzyme-Linked Immunosorbent Assay for Detecting Neutralizing Antibodies against Foot-and-Mouth Disease Virus Serotype O

2019 ◽  
Vol 57 (12) ◽  
Author(s):  
Yimei Cao ◽  
Kun Li ◽  
Sheng Wang ◽  
Yuanfang Fu ◽  
Pu Sun ◽  
...  
Keyword(s):  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Neutralizing Antibody ◽  
Mouth Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serotype O ◽  
Fmdv Serotype ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Vaccination with inactivated vaccines is still the main measure to control foot-and-mouth disease (FMD) in areas where the disease is endemic, and the level of neutralizing antibody in vaccinated animals is directly related to their protection against virus challenge. Currently, neutralizing antibody is mainly detected using the virus neutralization test (VNT) based on cell culture, which is laborious and time-consuming and requires restrictive biocontainment facilities. In this study, two broadly neutralizing antibodies (bnAbs), E46 and F128, were successfully produced using techniques for the isolation of single B cells from peripheral blood mononuclear cells (PBMCs) from bovines sequentially immunized with three topotypes of foot-and-mouth disease virus (FMDV) serotype O. Based on these bnAbs, a blocking enzyme-linked immunosorbent assay (ELISA) for detecting neutralizing antibodies (NA-ELISA) against FMDV serotype O was developed. The specificity and sensitivity of the test were estimated to be 99.21% and 100%, respectively. A significant correlation (P < 0.01) was observed between the NA-ELISA titers and the VNT titers for all sera from vaccinated animals and for all tested strains, suggesting that the NA-ELISA could detect neutralizing antibodies against FMDV serotype O strains of wide antigenic and molecular diversity and could be used for the evaluation of protective immunity.

scholarly journals Induction of a Cross-Reactive CD8+ T Cell Response following Foot-and-Mouth Disease Virus Vaccination

2010 ◽  
Vol 84 (23) ◽  
pp. 12375-12384 ◽  
Author(s):  
Efrain Guzman ◽  
Geraldine Taylor ◽  
Bryan Charleston ◽  
Shirley A. Ellis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Serotype O ◽  
Fmdv Serotype ◽  
Fmdv Serotypes ◽  
Mouth Disease Virus ◽  
Ifn Γ

ABSTRACT Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. Current inactivated FMDV vaccines generate short-term, serotype-specific protection, mainly through neutralizing antibody. An improved understanding of the mechanisms of protective immunity would aid design of more effective vaccines. We have previously reported the presence of virus-specific CD8+ T cells in FMDV-vaccinated and -infected cattle. In the current study, we aimed to identify CD8+ T cell epitopes in FMDV recognized by cattle vaccinated with inactivated FMDV serotype O. Analysis of gamma interferon (IFN-γ)-producing CD8+ T cells responding to stimulation with FMDV-derived peptides revealed one putative CD8+ T cell epitope present within the structural protein P1D, comprising residues 795 to 803 of FMDV serotype O UKG/2001. The restricting major histocompatibility complex (MHC) class I allele was N*02201, expressed by the A31 haplotype. This epitope induced IFN-γ release, proliferation, and target cell killing by αβ CD8+ T cells, but not CD4+ T cells. A protein alignment of representative samples from each of the 7 FMDV serotypes showed that the putative epitope is highly conserved. CD8+ T cells from FMDV serotype O-vaccinated A31+ cattle recognized antigen-presenting cells (APCs) loaded with peptides derived from all 7 FMDV serotypes, suggesting that CD8+ T cells recognizing the defined epitope are cross-reactive to equivalent peptides derived from all of the other FMDV serotypes.

scholarly journals Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells

Virology ◽  
2017 ◽  
Vol 512 ◽  
pp. 132-143 ◽  
Author(s):  
Anna Kloc ◽  
Fayna Diaz-San Segundo ◽  
Elizabeth A. Schafer ◽  
Devendra K. Rai ◽  
Mary Kenney ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Virus ◽  
Innate Immune Response ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Mouth Disease Virus ◽  
Foot And Mouth
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