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Identification of differentially expressed miRNAs in human cells infected with different Zika virus strains

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Abstract

Infection with distinct Zika virus (ZIKV) strains in in vitro and in vivo models has demonstrated that the host’s response to infection is strain-dependent. There has been no analysis of the impact of infection with different ZIKV strains on miRNA expression in human cells. We investigated miRNA expression in PNT1A cells upon infection with an African ZIKV strain (MR766) and a Brazilian ZIKV strain (ZIKVBR) using PCR array. Sixteen miRNAs were modulated in PNT1A cells: six miRNAs were modulated by both strains, while a set of ten miRNAs were modulated exclusively by ZIKVBR infection. In silico analysis showed that nine significant KEGG pathways and eight significant GO terms were predicted to be enriched upon ZIKVBR infection, and these pathways were related to cancer, environmental information processing, metabolism, and extracellular matrix. Differential modulation of miRNA expression suggests that distinct strains of ZIKV can differentially modulate the host response through the action of miRNAs.

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References

  1. Dick GW, Kitchen SF, Haddow AJ (1952) Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hygi 46(5):509–520

    Article  CAS  Google Scholar 

  2. Passi D, Sharma S, Dutta SR, Ahmed M (2017) Zika virus diseases—the new face of an ancient enemy as global public health emergency (2016): brief review and recent updates. Int J Prev Med 8:6

    Article  PubMed  PubMed Central  Google Scholar 

  3. Reagan-Steiner S, Simeone R, Simon E, Bhatnagar J, Oduyebo T, Free R, Denison AM, Rabeneck DB, Ellington S, Petersen E, Gary J, Hale G, Keating MK, Martines RB, Muehlenbachs A, Ritter J, Lee E, Davidson A, Conners E, Scotland S, Sandhu K, Bingham A, Kassens E, Smith L, St George K, Ahmad N, Tanner M, Beavers S, Miers B, VanMaldeghem K, Khan S, Rabe I, Gould C, Meaney-Delman D, Honein MA, Shieh WJ, Jamieson DJ, Fischer M, Zaki SR, U.S.Z.P.R. Collaboration, E. Zika Virus Response, T. Surveillance Task Force Pathology (2017) Evaluation of placental and fetal tissue specimens for Zika virus infection—50 states and district of Columbia, January–December, 2016. MMWR Morb Mortal Wkly Rep 66(24):636–643

    Article  PubMed  PubMed Central  Google Scholar 

  4. Beaver JT, Lelutiu N, Habib R, Skountzou I (2018) Evolution of two major Zika virus lineages: implications for pathology immune response, and vaccine development. Front Immunol 9:1640

    Article  PubMed  PubMed Central  Google Scholar 

  5. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB (2009) Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 360(24):2536–2543

    Article  CAS  PubMed  Google Scholar 

  6. Cao-Lormeau VM, Roche C, Teissier A, Robin E, Berry AL, Mallet HP, Sall AA, Musso D (2014) Zika virus, French polynesia, South pacific, 2013. Emerg Infect Dis 20(6):1085–1086

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, Dub T, Baudouin L, Teissier A, Larre P, Vial AL, Decam C, Choumet V, Halstead SK, Willison HJ, Musset L, Manuguerra JC, Despres P, Fournier E, Mallet HP, Musso D, Fontanet A, Neil J, Ghawche F (2016) Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 387(10027):1531–1539

    Article  PubMed  PubMed Central  Google Scholar 

  8. Brasil P, Pereira JP Jr, Moreira ME, Nogueira RMR, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, Zin AA, Horovitz D, Daltro P, Boechat M, Raja Gabaglia C, de Sequeira PC, Pilotto JH, Medialdea-Carrera R, Cotrim da Cunha D, de Carvalho LMA, Pone M, Siqueira AM, Calvet GA, Baiao AER, Neves ES, de Carvalho PRN, Hasue RH, Marschik PB, Einspieler C, Janzen C, Cherry JD, de Filippis AMB, Nielsen-Saines K (2016) Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 375(24):2321–2334

    Article  PubMed  PubMed Central  Google Scholar 

  9. Brasil P, Sequeira PC, Freitas AD, Zogbi HE, Calvet GA, de Souza RV, Siqueira AM, de Mendonca MC, Nogueira RM, de Filippis AM, Solomon T (2016) Guillain-Barre syndrome associated with Zika virus infection. Lancet 387(10026):1482

    Article  PubMed  Google Scholar 

  10. Ye Q, Liu ZY, Han JF, Jiang T, Li XF, Qin CF (2016) Genomic characterization and phylogenetic analysis of Zika virus circulating in the Americas. Infect Genet Evol 43:43–49

    Article  CAS  PubMed  Google Scholar 

  11. Smith DR, Sprague TR, Hollidge BS, Valdez SM, Padilla SL, Bellanca SA, Golden JW, Coyne SR, Kulesh DA, Miller LJ, Haddow AD, Koehler JW, Gromowski GD, Jarman RG, Alera MTP, Yoon IK, Buathong R, Lowen RG, Kane CD, Minogue TD, Bavari S, Tesh RB, Weaver SC, Linthicum KJ, Pitt ML, Nasar F (2018) African and Asian Zika virus isolates display phenotypic differences both in vitro and in vivo. Am J Trop Med Hyg 98(2):432–444

    Article  CAS  PubMed  Google Scholar 

  12. Simonin Y, van Riel D, Van de Perre P, Rockx B, Salinas S (2017) Differential virulence between Asian and African lineages of Zika virus. PLoS Negl Trop Dis 11(9):e0005821

    Article  PubMed  PubMed Central  Google Scholar 

  13. Simonin Y, Loustalot F, Desmetz C, Foulongne V, Constant O, Fournier-Wirth C, Leon F, Moles JP, Goubaud A, Lemaitre JM, Maquart M, Leparc-Goffart I, Briant L, Nagot N, Van de Perre P, Salinas S (2016) Zika virus strains potentially display different infectious profiles in human neural cells. EBioMedicine 12:161–169

    Article  PubMed  PubMed Central  Google Scholar 

  14. Goodfellow FT, Willard KA, Wu X, Scoville S, Stice SL, Brindley MA (2018) Strain-dependent consequences of Zika virus infection and differential impact on neural development. Viruses 10(10):550–564

    Article  PubMed Central  Google Scholar 

  15. Duggal NK, Ritter JM, McDonald EM, Romo H, Guirakhoo F, Davis BS, Chang GJ, Brault AC (2017) Differential neurovirulence of African and Asian genotype Zika virus isolates in outbred immunocompetent mice. Am J Trop Med Hyg 97(5):1410–1417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449(7164):919–922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhu X, He Z, Hu Y, Wen W, Lin C, Yu J, Pan J, Li R, Deng H, Liao S, Yuan J, Wu J, Li J, Li M (2014) MicroRNA-30e* suppresses dengue virus replication by promoting NF-kappaB-dependent IFN production. PLoS Negl Trop Dis 8(8):e3088

    Article  PubMed  PubMed Central  Google Scholar 

  18. Slonchak A, Shannon RP, Pali G, Khromykh AA (2015) Human MicroRNA miR-532-5p exhibits antiviral activity against West Nile virus via suppression of host genes SESTD1 and TAB3 required for virus replication. J Virol 90(5):2388–2402

    Article  PubMed  Google Scholar 

  19. Escalera-Cueto M, Medina-Martinez I, del Angel RM, Berumen-Campos J, Gutierrez-Escolano AL, Yocupicio-Monroy M (2015) Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells. Virus Res 196:105–112

    Article  CAS  PubMed  Google Scholar 

  20. Ferreira RN, Holanda GM, Pinto Silva EV, Casseb SMM, Melo KFL, Carvalho CAM, Lima JA, Vasconcelos PFC, Cruz ACR (2018) Zika virus alters the expression profile of microRNA-related genes in liver, lung, and kidney cell lineages. Viral Immunol 31(8):583–588

    Article  CAS  PubMed  Google Scholar 

  21. Kozak RA, Majer A, Biondi MJ, Medina SJ, Goneau LW, Sajesh BV, Slota JA, Zubach V, Severini A, Safronetz D, Hiebert SL, Beniac DR, Booth TF, Booth SA, Kobinger GP (2017) MicroRNA and mRNA dysregulation in astrocytes infected with Zika virus. Viruses 9(10):297–314

    Article  PubMed Central  Google Scholar 

  22. Dang JW, Tiwari SK, Qin Y, Rana TM (2019) Genome-wide integrative analysis of Zika-virus-infected neuronal stem cells reveals roles for MicroRNAs in cell cycle and stemness. Cell Rep 27(12):3618-3628 e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Faria NR et al (2016) Zika virus in the Americas: Early epidemiological and genetic findings. Science 352(6283):345–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fields BN, Knipe DM, Howley PM (1996) Fundamental virology, 3rd edn. Lippincott-Raven, Philadelphia

    Google Scholar 

  25. Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR (2008) Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 14(8):1232–1239

    Article  Google Scholar 

  26. Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res gkv403

  27. Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Vlachos IS, Paraskevopoulou MD, Karagkouni D, Georgakilas G, Vergoulis T, Kanellos I, Anastasopoulos I, Maniou S, Karathanou K, Kalfakakou D, Fevgas A, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions. Nucleic Acids Res 43(Database issue):D153-9

  29. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25(8):1091–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Spencer JL, Lahon A, Tran LL, Arya RP, Kneubehl AR, Vogt MB, Xavier D, Rowley DR, Kimata JT, Rico-Hesse RR (2018) Replication of Zika virus in human prostate cells: a potential source of sexually transmitted virus. J Infect Dis 217(4):538–547

    Article  CAS  PubMed  Google Scholar 

  32. Moran J, Ramirez-Martinez G, Jimenez-Alvarez L, Cruz A, Perez-Patrigeon S, Hidalgo A, Orozco L, Martinez A, Padilla-Noriega L, Avila-Moreno F, Cabello C, Granados J, Ortiz-Quintero B, Ramirez-Venegas A, Ruiz-Palacios GM, Zlotnik A, Merino E, Zuniga J (2015) Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection. Exp Mol Pathol 99(2):253–261

    Article  CAS  PubMed  Google Scholar 

  33. Goswami S, Banerjee A, Kumari B, Bandopadhyay B, Bhattacharya N, Basu N, Vrati S, Banerjee A (2017) Differential expression and significance of circulating microRNAs in cerebrospinal fluid of acute encephalitis patients infected with japanese encephalitis virus. Mol Neurobiol 54(2):1541–1551

    Article  CAS  PubMed  Google Scholar 

  34. Zhou B, Wang S, Mayr C, Bartel DP, Lodish HF (2007) miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci USA 104(17):7080–7085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, Rajewsky N, Bender TP, Rajewsky K (2007) MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131(1):146–159

    Article  CAS  PubMed  Google Scholar 

  36. Tsitsiou E, Lindsay MA (2009) microRNAs and the immune response. Curr Opin Pharmacol 9(4):514–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S, Mussolin L, Ruggero K, Bonanno L, Guffanti A, De Bellis G, Gerosa G, Stellin G, D’Agostino DM, Basso G, Bronte V, Indraccolo S, Amadori A, Zanovello P (2011) Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood 117(26):7053–7062

    Article  CAS  PubMed  Google Scholar 

  38. Zheng Q, Zhou L, Mi QS (2012) MicroRNA miR-150 is involved in Valpha14 invariant NKT cell development and function. J Immunol 188(5):2118–2126

    Article  CAS  PubMed  Google Scholar 

  39. Santangelo L, Bordoni V, Montaldo C, Cimini E, Zingoni A, Battistelli C, D’Offizi G, Capobianchi MR, Santoni A, Tripodi M, Agrati C (2018) Hepatitis C virus direct-acting antivirals therapy impacts on extracellular vesicles microRNAs content and on their immunomodulating properties. Liver Int 38(10):1741–1750

    Article  CAS  PubMed  Google Scholar 

  40. Delafiori J, Lima EO, Dabaja MZ, Dias-Audibert FL, de Oliveira DN, Melo C, Morishita KN, Sales GM, Ruiz A, da Silva GG, Lancellotti M, Catharino RR (2019) Molecular signatures associated with prostate cancer cell line (PC-3) exposure to inactivated Zika virus. Sci Rep 9(1):15351

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, Fernandez E, Richner JM, Zhang R, Shan C, Tycksen E, Wang X, Shi PY, Diamond MS, Rich JN, Chheda MG (2017) Zika virus has oncolytic activity against glioblastoma stem cells. J Exp Med 214(10):2843–2857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tomlin H, Piccinini AM (2018) A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens. Immunology 155(2):186–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Aid M, Abbink P, Larocca RA, Boyd M, Nityanandam R, Nanayakkara O, Martinot AJ, Moseley ET, Blass E, Borducchi EN, Chandrashekar A, Brinkman AL, Molloy K, Jetton D, Tartaglia LJ, Liu J, Best K, Perelson AS, De La Barrera RA, Lewis MG, Barouch DH (2017) Zika Virus persistence in the central nervous system and lymph nodes of Rhesus monkeys. Cell 169(4):610–620 e14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the São Paulo Research Foundation (FAPESP, grant numbers: 2017/09197-2; 2014/22198-0; 2015/16660-5) and “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq, grant number: 440723/2016-7).

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Correspondence to Marilia Freitas Calmon.

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Machado, F.C., Bittar, C., Rahal, P. et al. Identification of differentially expressed miRNAs in human cells infected with different Zika virus strains. Arch Virol 166, 1681–1689 (2021). https://doi.org/10.1007/s00705-021-05051-9

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