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

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.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00018-09 ◽

2009 ◽

Vol 16 (8) ◽

pp. 1151-1157 ◽

Cited By ~ 25

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.

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Improvement of the immune response to foot and mouth disease virus vaccine in calves by using Avridine as adjuvant

Veterinary Immunology and Immunopathology ◽

10.1016/s0165-2427(99)00035-5 ◽

1999 ◽

Vol 69 (1) ◽

pp. 11-22 ◽

Cited By ~ 3

Author(s):

A.M Sadir ◽

P.I Zamorano ◽

A Romera ◽

A Wigdorovitz ◽

E Smitsaart ◽

...

Keyword(s):

Immune Response ◽

Disease Virus ◽

Virus Vaccine ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Mouth Disease Virus ◽

Foot And Mouth

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Immune response in cattle inoculated with the recombinant complete polyprotein of foot-and-mouth disease virus from Bombyx mori larvae

Chinese Science Bulletin ◽

10.1007/s11434-007-0436-1 ◽

2007 ◽

Vol 52 (20) ◽

pp. 2805-2810

Author(s):

ZhiYong Li ◽

YongZhu Yi ◽

XiangPing Yin ◽

ZhiFang Zhang ◽

JiXing Liu

Keyword(s):

Immune Response ◽

Bombyx Mori ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Mouth Disease Virus ◽

Foot And Mouth

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Selective Lymphocyte Depletion during the Early Stage of the Immune Response to Foot-and-Mouth Disease Virus Infection in Swine

Journal of Virology ◽

10.1128/jvi.80.5.2369-2379.2006 ◽

2006 ◽

Vol 80 (5) ◽

pp. 2369-2379 ◽

Cited By ~ 38

Author(s):

Fayna Díaz-San Segundo ◽

Francisco J. Salguero ◽

Ana de Avila ◽

M. Mar Fernández de Marco ◽

Miguel A. Sánchez-Martín ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Disease Virus ◽

Ex Vivo ◽

Early Stage ◽

Foot And Mouth Disease ◽

Analytical Techniques ◽

Mouth Disease ◽

Mouth Disease Virus ◽

Foot And Mouth

ABSTRACT Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves CD3+ CD4− CD8+/−, CD3+ CD4− CD8+Tc, and CD3+ CD4+ CD8+ memory Th but not CD3+ CD4+ CD8− naïve Th lymphocytes. In addition, a profound depletion of the vast majority of peripheral T cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion. Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV.

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