Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus

Yang, Bo; Zhang, Xiaohui; Zhang, Dajun; Hou, Jing; Xu, Guangyu; Sheng, Chaochao; Choudhury, Sk Mohiuddin; Zhu, Zixiang; Li, Dan; Zhang, Keshan; Zheng, Haixue; Liu, Xiangtao

doi:10.3390/pathogens9090729

Cited by 12 publications

(13 citation statements)

References 143 publications

(227 reference statements)

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“…Upon infection of the host, the virus will face an attack from the host immune response. In the battle with the host immune response, the virus has evolved a series of immune escape mechanisms to overcome the antiviral responses induced by the host immune system [ 31 ]. Although MDA5 is known to be responsible for picornavirus recognition [ 32 , 33 ], little is known about the interplay between MDA5 and FMDV.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…In addition, FMDV also damages the immune cells and inhibits the immune signal transduction, leading to the dysfunction of immune system and quick replication of the virus (26)(27)(28)(29). Many viral proteins have been identified to participate in disruption of host immune response, including both structural proteins and nonstructural proteins (9,10). Innate immunity is vital for guiding the adaptive immune response (30)(31)(32).…”

Section: Pathogenesis Of Fmdmentioning

confidence: 99%

“…FMDV has a short replication cycle in its host, and its virulence factors alter the host cell environment to promote viral replication by inactivating host factors and blocking their functions (108). A number of viral proteins of FMDV have been demonstrated to play suppressive roles on host immune response that ensures the replication of the virus in the host (9,10). These virulence factors inhibit host antiviral immune response by multiple manners which mainly include: suppression of synthesis of host proteins, blocking the synthesis of IFNs, and reducing the expression of IFNstimulated genes (ISGs) as well as proinflammatory cytokines.…”

Section: Suppression Of Antiviral Immune Response By Fmdv Virulence Factorsmentioning

confidence: 99%

“…Therefore, FMDV is an important pathogen that threatens the health of livestock. Two of our previous review papers have summarized how FMDV disrupts host RIG-I-like receptors pathway and type I interferon signaling (9,10). As for this review, we focused on the pathogenesis of FMD, FMDV receptors and cell tropism, innate/adaptive immune system dysfunction (how FMDV causes immune cell dysfunction), autophagy, apoptosis and Golgi-endoplasmic reticulum pathways in FMDV infection.…”

Section: Introductionmentioning

confidence: 99%

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Virus–Host Interactions in Foot-and-Mouth Disease Virus Infection

Wang

Yang

et al. 2021

Front. Immunol.

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Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, which has been regarded as a persistent challenge for the livestock industry in many countries. Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD that can spread rapidly by direct and indirect transmission. FMDV is internalized into host cell by the interaction between FMDV capsid proteins and cellular receptors. When the virus invades into the cells, the host antiviral system is quickly activated to suppress the replication of the virus and remove the virus. To retain fitness and host adaptation, various viruses have evolved multiple elegant strategies to manipulate host machine and circumvent the host antiviral responses. Therefore, identification of virus-host interactions is critical for understanding the host defense against virus infections and the pathogenesis of the viral infectious diseases. This review elaborates on the virus-host interactions during FMDV infection to summarize the pathogenic mechanisms of FMD, and we hope it can provide insights for designing effective vaccines or drugs to prevent and control the spread of FMD and other diseases caused by picornaviruses.

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“…Foot and mouth disease (FMD) is a highly contagious, devastating Disease and having economic impact with high morbidity rate in cloven-hoofed animals, including important livestock species such as cattle and buffalos (Alexandersen et al 2003; Thompson et al 2002;Yang et al 2020). Following FMD virus infection around 25% loss of productivity of infected animals was recorded including loss or reduction in animals' milk production (Bradhurst et al 2019;Ferrari et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic and Prophylactic Potential of FMD Virus-specific Polyvalent Immunoglobulins during an FMD Outbreak in Cattle

2021

Int J Vet Sci

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Foot and mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals worldwide. In the present study the therapeutic and prophylactic potential of polyclonal, polyvalent FMD virus-specific bovine antibodies has been investigated as a possible approach for rapid control, lessening of the severity of clinical signs and prophylactic protection of susceptible animals during FMD outbreaks. The prepared FMD virus-specific polyvalent immunoglobulins were concentrated, purified, filter sterilized (0.22nm) and its titer against the FMD virus serotypes, A, O and SAT2, was adjusted to 2.15, 2.25 and 2.10 log10 TCID50/ml, respectively. In an experimental FMDV induced infection, the immunoglobulin therapy was given 4 days post experimental infection. The effect of different doses of immunoglobulins (4, 6 and 8ml) the severity of the clinical signs, healing of lesions and virus shedding was determined. A dose of 8 ml (2.0 log10 TCID50/ml) of the prepared FMD virus-specific antibodies proved highly effective in reducing the severity of the clinical signs and inducing recovery within 48 - 96hrs post therapy, as compared with the control non-treated infected calves. A dose related recovery rate was recorded. Field trial was conducted and evaluated during the FMD outbreak in Egypt during 2016/2017. Significant reduction of the morbidity of the disease and 100% reduction of mortality were recorded. The prepared FMD virus-specific bovine polyvalent antibodies proved to be a drug of choice during FMD outbreaks protecting susceptible animals and inducing rapid recovery of diseased one associated with reducing clinical signs severity and reducing virus shedding.

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Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus

Cited by 12 publications

References 143 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

Virus–Host Interactions in Foot-and-Mouth Disease Virus Infection

Therapeutic and Prophylactic Potential of FMD Virus-specific Polyvalent Immunoglobulins during an FMD Outbreak in Cattle

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