Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa
Foot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the a...
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MDPI AG
2022-07-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/8/822 |
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| author | James J. Zhu Carolina Stenfeldt Elizabeth A. Bishop Jessica A. Canter Michael Eschbaumer Luis L. Rodriguez Jonathan Arzt |
| author_facet | James J. Zhu Carolina Stenfeldt Elizabeth A. Bishop Jessica A. Canter Michael Eschbaumer Luis L. Rodriguez Jonathan Arzt |
| author_sort | James J. Zhu |
| collection | DOAJ |
| description | Foot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the analysis of differentially expressed genes (DEG) identified during the transitional phase of infection, defined as the period when animals diverge between becoming carriers or terminators. During this phase, Th17-stimulating cytokines (IL6 and IL23A) and Th17-recruiting chemokines (CCL14 and CCL20) were upregulated in animals that were still infected (transitional carriers) compared to those that had recently cleared infection (terminators), whereas chemokines recruiting neutrophils and CD8+ T effector cells (CCL3 and ELR+CXCLs) were downregulated. Upregulated Th17-specific receptor, CCR6, and Th17-associated genes, CD146, MIR155, and ThPOK, suggested increased Th17 cell activity in transitional carriers. However, a complex interplay of the Th17 regulatory axis was indicated by non-significant upregulation of IL17A and downregulation of IL17F, two hallmarks of TH17 activity. Other DEG suggested that transitional carriers had upregulated aryl hydrocarbon receptor (AHR), non-canonical NFκB signaling, and downregulated canonical NFκB signaling. The results described herein provide novel insights into the mechanisms of establishment of FMDV persistence. Additionally, the fact that ruminants, unlike pigs, produce a large amount of AHR ligands suggests a plausible explanation of why FMDV persists in ruminants, but not in pigs. |
| first_indexed | 2024-03-09T03:59:35Z |
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| issn | 2076-0817 |
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| last_indexed | 2024-03-09T03:59:35Z |
| publishDate | 2022-07-01 |
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| series | Pathogens |
| spelling | doaj.art-877185524629479f9e8cfd83900c7b392023-12-03T14:15:09ZengMDPI AGPathogens2076-08172022-07-0111882210.3390/pathogens11080822Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal MucosaJames J. Zhu0Carolina Stenfeldt1Elizabeth A. Bishop2Jessica A. Canter3Michael Eschbaumer4Luis L. Rodriguez5Jonathan Arzt6Foreign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USAForeign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USAForeign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USAForeign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USAInstitute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, GermanyForeign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USAForeign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USAFoot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the analysis of differentially expressed genes (DEG) identified during the transitional phase of infection, defined as the period when animals diverge between becoming carriers or terminators. During this phase, Th17-stimulating cytokines (IL6 and IL23A) and Th17-recruiting chemokines (CCL14 and CCL20) were upregulated in animals that were still infected (transitional carriers) compared to those that had recently cleared infection (terminators), whereas chemokines recruiting neutrophils and CD8+ T effector cells (CCL3 and ELR+CXCLs) were downregulated. Upregulated Th17-specific receptor, CCR6, and Th17-associated genes, CD146, MIR155, and ThPOK, suggested increased Th17 cell activity in transitional carriers. However, a complex interplay of the Th17 regulatory axis was indicated by non-significant upregulation of IL17A and downregulation of IL17F, two hallmarks of TH17 activity. Other DEG suggested that transitional carriers had upregulated aryl hydrocarbon receptor (AHR), non-canonical NFκB signaling, and downregulated canonical NFκB signaling. The results described herein provide novel insights into the mechanisms of establishment of FMDV persistence. Additionally, the fact that ruminants, unlike pigs, produce a large amount of AHR ligands suggests a plausible explanation of why FMDV persists in ruminants, but not in pigs.https://www.mdpi.com/2076-0817/11/8/822foot-and-mouth disease virusFMDVpersistent infectionmicroarray analysisdifferential gene expressionpharyngeal epithelia |
| spellingShingle | James J. Zhu Carolina Stenfeldt Elizabeth A. Bishop Jessica A. Canter Michael Eschbaumer Luis L. Rodriguez Jonathan Arzt Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa Pathogens foot-and-mouth disease virus FMDV persistent infection microarray analysis differential gene expression pharyngeal epithelia |
| title | Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa |
| title_full | Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa |
| title_fullStr | Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa |
| title_full_unstemmed | Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa |
| title_short | Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa |
| title_sort | inferred causal mechanisms of persistent fmdv infection in cattle from differential gene expression in the nasopharyngeal mucosa |
| topic | foot-and-mouth disease virus FMDV persistent infection microarray analysis differential gene expression pharyngeal epithelia |
| url | https://www.mdpi.com/2076-0817/11/8/822 |
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