Host serum microRNA profiling during the early stage of foot-and-mouth disease virus infection
Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals, with many outbreaks in the developing world. MicroRNAs (miRNAs) are non-coding RNAs that regulate antiviral defence by post-transcriptional regulation of gene expression. In this study, the host miRNA response following FMDV infection was investigated in cattle, a natural host for FMDV. A significant alteration in serum miRNA expression was detected at early stages of infection. Compared to prior to infection, on day 2 postinfection (PI), 119 miRNAs were upregulated, of which 39 were significantly upregulated (P < 0.05). Gene target prediction and pathway enrichment analysis suggested that upregulated miRNAs target innate immune signalling pathways, suggesting a homeostasis effect, possibly to limit inappropriate immune responses. Further, for the significantly upregulated miRNAs, nine miRNA recognition elements were identified in the genome sequence of FMDV serotype O, which was used for infection. The antiviral effect of four of these miRNAs was confirmed in a cell culture system. These data demonstrate that changes in miRNA expression occur during early pathogenesis, and the identification of possible miRNA targets genes could help in elucidating molecular events involved in virus-host interaction and thus could be useful in developing therapeutic strategies.
We acknowledge the Director, ICAR-Indian Veterinary Research Institute (IVRI) Izatnagar, for facilitating this work. We are grateful to Dr. James Zhu, USDA, Plum Island Animal Disease Research Center, USA, for sharing the data on differentially regulated genes from acute FMDV infection. We thank the supporting staff of the IVRI animal facility for their assistance in care and handling of animals. We also acknowledge Genotypic Technology Private Limited Bengaluru for the microarray processing and assistance in analysis of the data.
Compliance with ethical standards
Conflict of interest
All of the authors declare that they have no conflict of interest.
The animal experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC) and carried out according to the guidelines of the Committee for the Purpose of Control and Supervision of Experiments in Animals (CPCSEA), Ministry of Environment, Forests and Climate Change, Government of India.
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