scholarly journals Innate Immune Defenses Induced by CpG Do Not Promote Vaccine-Induced Protection against Foot-and-Mouth Disease Virus in Pigs

2009 ◽  
Vol 16 (8) ◽  
pp. 1151-1157 ◽  
Author(s):  
M. P. Alves ◽  
L. Guzylack-Piriou ◽  
V. Juillard ◽  
J.-C. Audonnet ◽  
T. Doel ◽  
...  
Keyword(s):  
Disease Virus ◽  
Large Scale ◽  
Control Strategies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Noticeable Effect ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Natural Hosts

ABSTRACT Emergency vaccination as part of the control strategies against foot-and-mouth disease virus (FMDV) has the potential to limit virus spread and reduce large-scale culling. To reduce the time between vaccination and the onset of immunity, immunostimulatory CpG was tested for its capacity to promote early protection against FMDV challenge in pigs. To this end, CpG 2142, an efficient inducer of alpha interferon, was injected intramuscularly. Increased transcription of Mx1, OAS, and IRF-7 was identified as a sensitive measurement of CpG-induced innate immunity, with increased levels detectable to at least 4 days after injection of CpG formulated with Emulsigen. Despite this, CpG combined with an FMD vaccine did not promote protection. Pigs vaccinated 2 days before challenge had disease development, which was at least as acute as that of unvaccinated controls. All pigs vaccinated 7 days before challenge were protected without a noticeable effect of CpG. In summary, our results demonstrate the caution required when translating findings from mouse models to natural hosts of FMDV.

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 Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0190977 ◽  
Author(s):  
Lisbeth Ramirez-Carvajal ◽  
Steven J. Pauszek ◽  
Zaheer Ahmed ◽  
Umer Farooq ◽  
Khalid Naeem ◽  
...  
Keyword(s):  
Disease Virus ◽  
Genetic Stability ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Natural Hosts

scholarly journals Structures of Foot-and-mouth Disease Virus with neutralizing antibodies derived from recovered natural host reveal a mechanism for cross-serotype neutralization

2021 ◽  
Vol 17 (4) ◽  
pp. e1009507
Author(s):  
Yong He ◽  
Kun Li ◽  
Yimei Cao ◽  
Zixian Sun ◽  
Pinghua Li ◽  
...  
Keyword(s):  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Universal Vaccine ◽  
Isolation Technique ◽  
Serotype O ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Natural Hosts

The development of a universal vaccine against foot-and-mouth disease virus (FMDV) is hindered by cross-serotype antigenic diversity and by a lack of knowledge regarding neutralization of the virus in natural hosts. In this study, we isolated serotype O-specific neutralizing antibodies (NAbs) (F145 and B77) from recovered natural bovine hosts by using the single B cell antibody isolation technique. We also identified a serotype O/A cross-reacting NAb (R50) and determined virus-NAb complex structures by cryo-electron microscopy at near-atomic resolution. F145 and B77 were shown to engage the capsid of FMDV-O near the icosahedral threefold axis, binding to the BC/HI-loop of VP2. In contrast, R50 engages the capsids of both FMDV-O and FMDV-A between the 2- and 5-fold axes and binds to the BC/EF/GH-loop of VP1 and to the GH-loop of VP3 from two adjacent protomers, revealing a previously unknown antigenic site. The cross-serotype neutralizing epitope recognized by R50 is highly conserved among serotype O/A. These findings help to elucidate FMDV neutralization by natural hosts and provide epitope information for the development of a universal vaccine for cross-serotype protection against FMDV.

scholarly journals Foot-and-Mouth Disease Virus 3C Protease Cleaves NEMO To Impair Innate Immune Signaling

2012 ◽  
Vol 86 (17) ◽  
pp. 9311-9322 ◽  
Author(s):  
D. Wang ◽  
L. Fang ◽  
K. Li ◽  
H. Zhong ◽  
J. Fan ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Immune Signaling ◽  
3C Protease ◽  
Innate Immune Signaling ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Degradation of Nuclear Factor Kappa B during Foot-and-Mouth Disease Virus Infection

2007 ◽  
Vol 81 (23) ◽  
pp. 12803-12815 ◽  
Author(s):  
Teresa de los Santos ◽  
Fayna Diaz-San Segundo ◽  
Marvin J. Grubman
Keyword(s):  
Disease Virus ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Foot And Mouth Disease ◽  
Inhibitory Effect ◽  
Mouth Disease ◽  
Innate Immune ◽  
Nuclear Factor ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT We have previously shown that the leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV) interferes with the innate immune response by blocking the translation of interferon (IFN) protein and by reducing the immediate-early induction of beta IFN mRNA and IFN-stimulated genes. Here, we report that Lpro regulates the activity of nuclear factor κB (NF-κB). Analysis of NF-κB-dependent reporter gene expression in BHK-21 cells demonstrated that infection with wild-type (WT) virus has an inhibitory effect compared to infection with a genetically engineered mutant lacking the leader coding region. The expression of endogenous NF-κB-dependent genes tumor necrosis factor alpha and RANTES is also reduced in WT virus-infected primary porcine cells. This inhibitory effect is neither the result of a decrease in the level of the mRNA of p65/RelA, a subunit of NF-κB, nor a block on the nuclear translocation of p65/RelA, but instead appears to be a consequence of the degradation of accumulated p65/RelA. Viral Lpro is localized to the nucleus of infected cells, and there is a correlation between the translocation of Lpro and the decrease in the amount of nuclear p65/RelA. By using a recombinant cardiovirus expressing Lpro, we demonstrate that the disappearance of p65/RelA takes place in the absence of any other FMDV product. The observation that Lpro disrupts the integrity of NF-κB suggests a global mechanism by which FMDV antagonizes the cellular innate immune and inflammatory responses to viral infection.

scholarly journals Interferon-Induced Protection against Foot-and-Mouth Disease Virus Infection Correlates with Enhanced Tissue-Specific Innate Immune Cell Infiltration and Interferon-Stimulated Gene Expression

2009 ◽  
Vol 84 (4) ◽  
pp. 2063-2077 ◽  
Author(s):  
Fayna Diaz-San Segundo ◽  
Mauro P. Moraes ◽  
Teresa de los Santos ◽  
Camila C. A. Dias ◽  
Marvin J. Grubman
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Lymphoid Tissues ◽  
Type I ◽  
Oligoadenylate Synthetase ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Ifn Γ

ABSTRACT Previously, we demonstrated that type I interferon (IFN-α/β) or a combination of IFN-α/β and type II IFN (IFN-γ) delivered by a replication-defective human adenovirus 5 (Ad5) vector protected swine when challenged 1 day later with foot-and-mouth disease virus (FMDV). To gain a more comprehensive understanding of the mechanism of protection induced by IFNs, we inoculated groups of six swine with Ad5-vectors containing these genes, challenged 1 day later and euthanized 2 animals from each group prior to (1 day postinoculation [dpi]) and at 1 (2 dpi) and 6 days postchallenge (7 dpi). Blood, skin, and lymphoid tissues were examined for IFN-stimulated gene (ISG) induction and infiltration by innate immune cells. All IFN-inoculated animals had delayed and decreased clinical signs and viremia compared to the controls, and one animal in the IFN-α treated group did not develop disease. At 1 and 2 dpi the groups inoculated with the IFNs had increased numbers of dendritic cells and natural killer cells in the skin and lymph nodes, respectively, as well as increased levels of several ISGs compared to the controls. In particular, all tissues examined from IFN-treated groups had significant upregulation of the chemokine 10-kDa IFN-γ-inducible protein 10, and preferential upregulation of 2′,5′-oligoadenylate synthetase, Mx1, and indoleamine 2,3-dioxygenase. There was also upregulation of monocyte chemotactic protein 1 and macrophage inflammatory protein 3α in the skin. These data suggest that there is a complex interplay between IFN-induced immunomodulatory and antiviral activities in protection of swine against FMDV.

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