Chemiluminescence Immunoassay for the Detection of Antibodies against the 2C and 3ABC Nonstructural Proteins Induced by Infecting Pigs with Foot-and-Mouth Disease Virus

Liu, Zezhong; Shao, Jing; Zhao, Furong; Zhou, Gengxu; Gao, Shandian; Liu, Wei; Lv, Jing; Li, Xiumei; Li, Yangfan; Chang, Huiyun; Zhang, Yongguang

doi:10.1128/cvi.00153-17

Cited by 19 publications

(14 citation statements)

References 29 publications

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“…The FMDV causes foot-and-mouth disease (FMD), which is highly contagious in various cloven-hoofed animals, such as pigs, cows and goats [ 2 , 3 ]. The FMDV genome is 8.5 kb and consists of one open reading frame (ORF), which encodes a single polyprotein that is subsequently proteolyzed into four structural proteins (SPs: VP1, VP2, VP3 and VP4) and eight nonstructural proteins (NSPs: L pro , 2A, 2B, 2C, 3A, 3B, 3C pro and 3D) [ 2 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Choi

et al. 2021

Cells

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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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Section: Introductionmentioning

confidence: 99%

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

Kim

Choi

et al. 2021

Cells

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“…The FMD virus (FMDV), the causative agent of FMD, belongs to the Aphthovirus genus of the Picornaviridae family [2]. It has a positive-sense, single-stranded RNA genome that is translated into a polyprotein, which is further cleaved into structural proteins (SPs) and nonstructural proteins (NSPs) [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Application of Heparin Affinity Chromatography to Produce a Differential Vaccine without Eliciting Antibodies against the Nonstructural Proteins of the Serotype O Foot-and-Mouth Disease Viruses

Park

Lee

Kim

et al. 2020

Viruses

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Although polyethylene glycol (PEG) application is the most widely used method in removing nonstructural proteins (NSPs) for foot-and-mouth disease (FMD) vaccine production, some NSPs remaining in the antigen could elicit antibodies against these proteins after repeated vaccinations in livestock. Therefore, the purpose of this study was to purify the FMD virus (FMDV) via affinity chromatography using a heparin ligand to remove most proteins, including NSPs. Chromatography showed an intact virus (146S) particle recovery of 70% or more for three different strains of serotype O FMDV (two locally isolated strains and one genetically modified strain). The experimental vaccine made with antigens eluted via heparin affinity chromatography elicited virus-neutralizing antibodies against homologous viruses but did not induce antibodies against NSPs even after five immunizations in goats; this indicated that the NSPs were effectively removed from the vaccine antigen. This method can then be used to produce a higher-quality vaccine compared with PEG application in terms of the purity of the FMD vaccine. Therefore, this result would be an important groundwork for advanced FMD vaccine manufacturing in the near future.

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“…Recently, we have reported a new chemiluminescence immunoassay (CLIA) method to detect antibodies to both 3ABC and 2C with high sensitivity and shorter detection time (Liu et al., ). However, the use of full‐length 3ABC and 2C did not solve the high false‐positive rates caused by NSP contamination in the inactivated vaccine.…”

Section: Introductionmentioning

confidence: 99%

Development of a chemiluminescence immunoassay using recombinant non-structural epitope-based proteins to accurately differentiate foot-and-mouth disease virus-infected and vaccinated bovines

Liu

Zhao

Gao

et al. 2018

Transbound Emerg Dis

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The contamination of inactivated vaccine with non-structural proteins (NSPs) leads to a high false-positive rate, which is a substantial barrier to accurately differentiate foot-and-mouth disease virus (FMDV)-infected animals from vaccinated animals. To address this problem, a new chemiluminescence immunoassay (CLIA) method was developed to detect antibodies targeting the two recombinant epitope-based proteins located in 3A and 3B. The 3Aepitp-3Bepitp CLIA exhibited a diagnostic sensitivity of 94.0% and a diagnostic specificity of 97.5% for the detection of serum samples (naïve bovines, n = 52, vaccinated bovines, n = 422, infected bovines, n = 116) from animals with known status. The CLIA method also had a concordance rate of 88.1% with the PrioCHECK FMDV NSP ELISA based on the detection of 270 serum samples from the field. Importantly, the 3Aepitp-3Bepitp CLIA produced no false-positives when used to detect FMDV in samples from bovines that had been vaccinated up to five times, and it was demonstrated a low false-positive rate when the bovines had been vaccinated up to ten (2.15%) and fifteen times (5.93%). Therefore, the 3Aepitp-3Bepitp CLIA detects FMDV in samples from frequently vaccinated bovines with high accuracy and represents an alternative method to differentiate FMDV-infected and vaccinated bovines.

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Chemiluminescence Immunoassay for the Detection of Antibodies against the 2C and 3ABC Nonstructural Proteins Induced by Infecting Pigs with Foot-and-Mouth Disease Virus

Cited by 19 publications

References 29 publications

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

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

Application of Heparin Affinity Chromatography to Produce a Differential Vaccine without Eliciting Antibodies against the Nonstructural Proteins of the Serotype O Foot-and-Mouth Disease Viruses

Development of a chemiluminescence immunoassay using recombinant non-structural epitope-based proteins to accurately differentiate foot-and-mouth disease virus-infected and vaccinated bovines

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