Host serum microRNA profiling during the early stage of foot-and-mouth disease virus infection

  • Suresh H. Basagoudanavar
  • Madhusudan Hosamani
  • R. P. Tamil Selvan
  • B. P. Sreenivasa
  • Aniket Sanyal
  • R. Venkataramanan
Original Article

Abstract

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.

Notes

Acknowledgments

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.

Ethical approval

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.

Supplementary material

705_2018_3824_MOESM1_ESM.pdf (624 kb)
Supplementary material 1 (PDF 623 kb)
705_2018_3824_MOESM2_ESM.xls (181 kb)
Supplementary material 2 (XLS 181 kb)

References

  1. 1.
    Carrillo C, Tulman ER, Delhon G, Lu Z, Carreno A, Vagnozzi A, Kutish GF, Rock DL (2005) Comparative genomics of foot-and-mouth disease virus. J Virol 79(10):6487–6504.  https://doi.org/10.1128/JVI.79.10.6487-6504.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Carpenter TE, O’Brien JM, Hagerman AD, McCarl BA (2011) Epidemic and economic impacts of delayed detection of foot-and-mouth disease: a case study of a simulated outbreak in California. J Vet Diagn Invest 23(1):26–33.  https://doi.org/10.1177/104063871102300104 CrossRefPubMedGoogle Scholar
  3. 3.
    Samuel AR, Knowles NJ (2001) Foot-and-mouth disease type O viruses exhibit genetically and geographically distinct evolutionary lineages (topotypes). J Gen Virol 82(Pt 3):609–621.  https://doi.org/10.1099/0022-1317-82-3-609 CrossRefPubMedGoogle Scholar
  4. 4.
    Arzt J, Pacheco JM, Stenfeldt C, Rodriguez LL (2017) Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle. Virol J 14(1):89.  https://doi.org/10.1186/s12985-017-0758-9 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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. 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
  7. 7.
    Ahl R, Rump A (1976) Assay of bovine interferons in cultures of the porcine cell line IB-RS-2. Infect Immun 14(3):603–606PubMedPubMedCentralGoogle Scholar
  8. 8.
    Chinsangaram J, Moraes MP, Koster M, Grubman MJ (2003) Novel viral disease control strategy: adenovirus expressing alpha interferon rapidly protects swine from foot-and-mouth disease. J Virol 77(2):1621–1625CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bronevetsky Y, Ansel KM (2013) Regulation of miRNA biogenesis and turnover in the immune system. Immunol Rev 253(1):304–316.  https://doi.org/10.1111/imr.12059 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Melo CA, Melo SA (2014) Biogenesis and physiology of MicroRNAs. In: Fabbri M (ed) Non-coding RNAs and Cancer. Springer, New York, pp 5–24CrossRefGoogle Scholar
  11. 11.
    Lui PY, Jin DY, Stevenson NJ (2015) MicroRNA: master controllers of intracellular signaling pathways. Cell Mol Life Sci 72(18):3531–3542.  https://doi.org/10.1007/s00018-015-1940-0 CrossRefPubMedGoogle Scholar
  12. 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
  13. 13.
    Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, Saib A, Voinnet O (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308(5721):557–560.  https://doi.org/10.1126/science.1108784 CrossRefPubMedGoogle Scholar
  14. 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. 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. 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
  17. 17.
    Iguchi H, Kosaka N, Ochiya T (2010) Secretory microRNAs as a versatile communication tool. Commun Integr Biol 3(5):478–481.  https://doi.org/10.4161/cib.3.5.12693 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Correia CN, Nalpas NC, McLoughlin KE, Browne JA, Gordon SV, MacHugh DE, Shaughnessy RG (2017) Circulating microRNAs as potential biomarkers of infectious disease. Front Immunol 8:118.  https://doi.org/10.3389/fimmu.2017.00118 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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. 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. 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. 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
  23. 23.
    Reid SM, Ferris NP, Hutchings GH, Zhang Z, Belsham GJ, Alexandersen S (2002) Detection of all seven serotypes of foot-and-mouth disease virus by real-time, fluorogenic reverse transcription polymerase chain reaction assay. J Virol Methods 105(1):67–80CrossRefPubMedGoogle Scholar
  24. 24.
    Rodriguez-Calvo T, Diaz-San Segundo F, Sanz-Ramos M, Sevilla N (2011) A replication analysis of foot-and-mouth disease virus in swine lymphoid tissue might indicate a putative carrier stage in pigs. Vet Res 42:22.  https://doi.org/10.1186/1297-9716-42-22 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 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
  26. 26.
    Vejnar CE, Zdobnov EM (2012) MiRmap: comprehensive prediction of microRNA target repression strength. Nucleic Acids Res 40(22):11673–11683.  https://doi.org/10.1093/nar/gks901 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. Elife.  https://doi.org/10.7554/eLife.05005 Google Scholar
  28. 28.
    Mi H, Poudel S, Muruganujan A, Casagrande JT, Thomas PD (2016) PANTHER version 10: expanded protein families and functions, and analysis tools. Nucleic Acids Res 44(D1):D336–D342.  https://doi.org/10.1093/nar/gkv1194 CrossRefPubMedGoogle Scholar
  29. 29.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408.  https://doi.org/10.1006/meth.2001.1262 CrossRefPubMedGoogle Scholar
  30. 30.
    Bae IS, Chung KY, Yi J, Kim TI, Choi HS, Cho YM, Choi I, Kim SH (2015) Identification of reference genes for relative quantification of circulating microRNAs in bovine serum. PLoS One 10(3):e0122554.  https://doi.org/10.1371/journal.pone.0122554 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. American J Hygiene 27:493–497Google Scholar
  32. 32.
    Lawless N, Vegh P, O’Farrelly C, Lynn DJ (2014) The Role of microRNAs in Bovine Infection and Immunity. Front Immunol 5:611.  https://doi.org/10.3389/fimmu.2014.00611 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Arzt J, Pacheco JM, Rodriguez LL (2010) The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation. Identification of the nasopharynx as the primary site of infection. Vet Pathol 47(6):1048–1063.  https://doi.org/10.1177/0300985810372509 CrossRefPubMedGoogle Scholar
  34. 34.
    Turchinovich A, Weiz L, Langheinz A, Burwinkel B (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res 39(16):7223–7233.  https://doi.org/10.1093/nar/gkr254 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kroh EM, Parkin RK, Mitchell PS, Tewari M (2010) Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 50(4):298–301.  https://doi.org/10.1016/j.ymeth.2010.01.032 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Li LM, Hu ZB, Zhou ZX, Chen X, Liu FY, Zhang JF, Shen HB, Zhang CY, Zen K (2010) Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res 70(23):9798–9807.  https://doi.org/10.1158/0008-5472.CAN-10-1001 CrossRefPubMedGoogle Scholar
  37. 37.
    van der Spek PJ, Kremer A, Murry L, Walker MG (2003) Are gene expression microarray analyses reliable? A review of studies of retinoic acid responsive genes. Genom Proteom Bioinform 1(1):9–14CrossRefGoogle Scholar
  38. 38.
    Morey JS, Ryan JC, Van Dolah FM (2006) Microarray validation: factors influencing correlation between oligonucleotide microarrays and real-time PCR. Biol Proced Online 8:175–193.  https://doi.org/10.1251/bpo126 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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
  40. 40.
    Liu Q, Zhou YH, Yang ZQ (2016) The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol 13(1):3–10.  https://doi.org/10.1038/cmi.2015.74 CrossRefPubMedGoogle Scholar
  41. 41.
    Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG (2012) Into the eye of the cytokine storm. Microbiol Mol Biol Rev 76(1):16–32.  https://doi.org/10.1128/MMBR.05015-11 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Aguado LC, Schmid S, Sachs D, Shim JV, Lim JK, tenOever BR (2015) microRNA function is limited to cytokine control in the acute response to virus infection. Cell Host Microbe 18(6):714–722.  https://doi.org/10.1016/j.chom.2015.11.003 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zhu JJ, Arzt J, Puckette MC, Smoliga GR, Pacheco JM, Rodriguez LL (2013) Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression. PLoS One 8(5):e64119.  https://doi.org/10.1371/journal.pone.0064119 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Knowlton KU, Badorff C (1999) The immune system in viral myocarditis: maintaining the balance. Circ Res 85(6):559–561CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.FMD Vaccine Research LaboratoryICAR-Indian Veterinary Research InstituteBengaluruIndia

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