Host serum microRNA profiling during the early stage of foot-and-mouth disease virus infection
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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.
- 5.Arzt J, Pacheco JM, Smoliga GR, Tucker MT, Bishop E, Pauszek SJ, Hartwig EJ, de los Santos T, Rodriguez LL (2014) Foot-and-mouth disease virus virulence in cattle is co-determined by viral replication dynamics and route of infection. Virology 452–453:12–22. https://doi.org/10.1016/j.virol.2014.01.001 CrossRefPubMedGoogle Scholar
- 6.Moraes MP, de Los Santos T, Koster M, Turecek T, Wang H, Andreyev VG, Grubman MJ (2007) Enhanced antiviral activity against foot-and-mouth disease virus by a combination of type I and II porcine interferons. J Virol 81(13):7124–7135. https://doi.org/10.1128/JVI.02775-06 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Skalsky RL, Cullen BR (2010) Viruses, microRNAs, and host interactions. Annu Rev Microbiol 64:123–141. https://doi.org/10.1146/annurev.micro.112408.134243 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Scheel TK, Luna JM, Liniger M, Nishiuchi E, Rozen-Gagnon K, Shlomai A, Auray G, Gerber M, Fak J, Keller I, Bruggmann R, Darnell RB, Ruggli N, Rice CM (2016) A broad RNA virus survey reveals both miRNA dependence and functional sequestration. Cell Host Microbe 19(3):409–423. https://doi.org/10.1016/j.chom.2016.02.007 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Zhang KS, Liu YJ, Kong HJ, Cheng WW, Shang YJ, Tian H, Zheng HX, Guo JH, Liu XT (2014) Identification and analysis of differential miRNAs in PK-15 cells after foot-and-mouth disease virus infection. PLoS One 9(3):e90865. https://doi.org/10.1371/journal.pone.0090865 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Du J, Guo X, Gao S, Luo J, Gong X, Hao C, Yang B, Lin T, Shao J, Cong G, Chang H (2014) Induction of protection against foot-and-mouth disease virus in cell culture and transgenic suckling mice by miRNA targeting integrin alphav receptor. J Biotechnol 187:154–161. https://doi.org/10.1016/j.jbiotec.2014.07.001 CrossRefPubMedGoogle Scholar
- 19.Stenfeldt C, Arzt J, Smoliga G, LaRocco M, Gutkoska J, Lawrence P (2017) Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection. Virol J 14(1):71. https://doi.org/10.1186/s12985-017-0743-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Chase-Topping ME, Handel I, Bankowski BM, Juleff ND, Gibson D, Cox SJ, Windsor MA, Reid E, Doel C, Howey R, Barnett PV, Woolhouse ME, Charleston B (2013) Understanding foot-and-mouth disease virus transmission biology: identification of the indicators of infectiousness. Vet Res 44:46. https://doi.org/10.1186/1297-9716-44-46 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.OIE (2017) Foot-and-mouth disease. In: Manual of diagnostic tests and vaccines for terrestrial animals. World organization for animal health web. http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.08_FMD.pdf. Accessed 31 Mar 2018
- 22.Hosamani M, Basagoudanavar SH, Tamil Selvan RP, Das V, Ngangom P, Sreenivasa BP, Hegde R, Venkataramanan R (2015) A multi-species indirect ELISA for detection of non-structural protein 3ABC specific antibodies to foot-and-mouth disease virus. Arch Virol 160(4):937–944. https://doi.org/10.1007/s00705-015-2339-9 CrossRefPubMedGoogle Scholar
- 25.Basagoudanavar SH, Hosamani M, Tamil Selvan RP, Sreenivasa BP, Saravanan P, Chandrasekhar Sagar BK, Venkataramanan R (2013) Development of a liquid-phase blocking ELISA based on foot-and-mouth disease virus empty capsid antigen for seromonitoring vaccinated animals. Arch Virol 158(5):993–1001. https://doi.org/10.1007/s00705-012-1567-5 CrossRefPubMedGoogle Scholar
- 31.Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. American J Hygiene 27:493–497Google Scholar
- 39.Caballero IS, Honko AN, Gire SK, Winnicki SM, Mele M, Gerhardinger C, Lin AE, Rinn JL, Sabeti PC, Hensley LE, Connor JH (2016) In vivo Ebola virus infection leads to a strong innate response in circulating immune cells. BMC Genom 17:707. https://doi.org/10.1186/s12864-016-3060-0 CrossRefGoogle Scholar