Advertisement

Virus Genes

pp 1–5 | Cite as

The BeWo cell line derived from a human placental choriocarcinoma is permissive for respiratory syncytial virus infection

  • M. A. Velázquez-Cervantes
  • M. Martínez-Castillo
  • L. D. González-García
  • T. A. Vargas-Pavía
  • M. G. Martínez-Salazar
  • I. Mancilla-Herrera
  • G. León-Reyes
  • J. García-Cordero
  • A. C. Helguera-Repetto
  • M. León-JuárezEmail author
Article

Abstract

The respiratory syncytial virus (RSV) is the main pathogen associated with upper respiratory tract infections during early childhood. Vertical transmission of this virus has been suggested in humans, based on observations recorded during animal studies that revealed an association of RSV with persistent structural and functional changes in the developing lungs of the offspring. However, human placentas have not yet been evaluated for susceptibility to RSV infection. In this study, we examined the capacity of RSV to infect a human trophoblast model, the BeWo cell line. Our results suggest that BeWo cells are susceptible to RSV infection since they allow RNA viral replication, viral protein translation, leading to the production of infectious RSV particles. In this report, we demonstrate that a human placenta model system, consisting of BeWo cells, is permissive to RSV infection. Thus, the BeWo cell line may represent a useful model for studies that aim to characterize the events of a possible RSV infection at the human maternal–fetal interface.

Keywords

Respiratory syncytial virus BeWo cells Trophoblast Placenta Viral cycle replication 

Notes

Acknowledgements

We are grateful to Dr. Beatriz Gomez (UNAM), Dr. Alberto Guzman (INPer), Dra. Veronica Zaga Clavellina (INPer), Dr. Lorena Gutierrez (Cinvestav), and Dr. Yonathan Garfias (UNAM) for the antibodies, cells, and viruses donated for this study. This research was supported by the National Council on Science and Technology CONACYT (CB-2015-01-255007 to M.L.J.) and Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes” (212250-3210-21007-03-15 to M.L.J.). L.D.G.G. received a fellowship from CONACYT. Additionally, M.L.J., M.H.I., G.C.J., and H.R.A.C. acknowledge their membership of the National System of Researchers (SNI).

Author contributions

Conceived and designed the experiments: MAVC, JGC, HRAC, and MLJ. Performed the experiments: MAVC, LDGG, TAVP, MSMG and MHI. Contributed reagents/materials/analysis tools: MHI and HRAC. Wrote the paper: MLJ, MMC, and GLR. Coordinated and facilitated the project: MLJ. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

All authors declare that no conflicts of interest exist.

Research involving human participants or animals

This article does not contain any study with human participants or animals, performed by any of the authors.

References

  1. 1.
    Fauroux B, Simoes EAF, Checchia PA, Paes B, Figueras-Aloy J, Manzoni P, Bont L, Carbonell-Estrany X (2017) The burden and long-term respiratory morbidity associated with respiratory syncytial virus infection in early childhood. Infect Dis Ther 6(2):173–197.  https://doi.org/10.1007/s40121-017-0151-4 CrossRefGoogle Scholar
  2. 2.
    Arnold R, Konig W (2005) Respiratory syncytial virus infection of human lung endothelial cells enhances selectively intercellular adhesion molecule-1 expression. J Immunol 174(11):7359–7367CrossRefGoogle Scholar
  3. 3.
    Li XQ, Fu ZF, Alvarez R, Henderson C, Tripp RA (2006) Respiratory syncytial virus (RSV) infects neuronal cells and processes that innervate the lung by a process involving RSV G protein. J Virol 80(1):537–540.  https://doi.org/10.1128/JVI.80.1.537-540.2006 CrossRefGoogle Scholar
  4. 4.
    Rivera-Toledo E, Gomez B (2012) Respiratory syncytial virus persistence in macrophages alters the profile of cellular gene expression. Viruses 4(12):3270–3280CrossRefGoogle Scholar
  5. 5.
    Angel Rico M, Trento A, Ramos M, Johnstone C, Del Val M, Melero JA, Lopez D (2009) Human respiratory syncytial virus infects and induces activation markers in mouse B lymphocytes. Immunol Cell Biol 87(4):344–350.  https://doi.org/10.1038/icb.2008.109 CrossRefGoogle Scholar
  6. 6.
    Eisenhut M (2006) Extrapulmonary manifestations of severe respiratory syncytial virus infection—a systematic review. Crit Care 10(4):R107.  https://doi.org/10.1186/cc4984 CrossRefGoogle Scholar
  7. 7.
    Esposito S, Salice P, Bosis S, Ghiglia S, Tremolati E, Tagliabue C, Gualtieri L, Barbier P, Galeone C, Marchisio P, Principi N (2010) Altered cardiac rhythm in infants with bronchiolitis and respiratory syncytial virus infection. BMC Infect Dis 10:305.  https://doi.org/10.1186/1471-2334-10-305 CrossRefGoogle Scholar
  8. 8.
    Delorme-Axford E, Sadovsky Y, Coyne CB (2014) The placenta as a barrier to viral infections. Annu Rev Virol 1(1):133–146.  https://doi.org/10.1146/annurev-virology-031413-085524 CrossRefGoogle Scholar
  9. 9.
    Piedimonte G, Walton C, Samsell L (2013) Vertical transmission of respiratory syncytial virus modulates pre- and postnatal innervation and reactivity of rat airways. PLoS ONE 8(4):e61309.  https://doi.org/10.1371/journal.pone.0061309 CrossRefGoogle Scholar
  10. 10.
    Brown PM, Harford TJ, Agrawal V, Yen-Lieberman B, Rezaee F, Piedimonte G (2017) Prenatal exposure to respiratory syncytial virus alters postnatal immunity and airway smooth muscle contractility during early-life reinfections. PLoS ONE 12(2):e0168786.  https://doi.org/10.1371/journal.pone.0168786 CrossRefGoogle Scholar
  11. 11.
    Rezaee F, Gibson LF, Piktel D, Othumpangat S, Piedimonte G (2011) Respiratory syncytial virus infection in human bone marrow stromal cells. Am J Respir Cell Mol Biol 45(2):277–286.  https://doi.org/10.1165/rcmb.2010-0121OC CrossRefGoogle Scholar
  12. 12.
    Rohwedder A, Keminer O, Forster J, Schneider K, Schneider E, Werchau H (1998) Detection of respiratory syncytial virus RNA in blood of neonates by polymerase chain reaction. J Med Virol 54(4):320–327CrossRefGoogle Scholar
  13. 13.
    Fonceca AM, Chopra A, Levy A, Noakes PS, Poh MW, Bear NL, Prescott S, Everard ML (2017) Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months. PLoS ONE 12(4):e0173738.  https://doi.org/10.1371/journal.pone.0173738 CrossRefGoogle Scholar
  14. 14.
    Bhat P, Anderson DA (2007) Hepatitis B virus translocates across a trophoblastic barrier. J Virol 81(13):7200–7207.  https://doi.org/10.1128/JVI.02371-06 CrossRefGoogle Scholar
  15. 15.
    Tzang BS, Chiang SY, Chan HC, Liu CH, Hsu TC (2016) Human parvovirus B19 antibodies induce altered membrane protein expression and apoptosis of BeWo trophoblasts. Mol Med Rep 14(5):4399–4406.  https://doi.org/10.3892/mmr.2016.5787 CrossRefGoogle Scholar
  16. 16.
    Huang Q, Chen H, Wang F, Brost BC, Li J, Gao Y, Li Z, Gao Y, Jiang SW (2014) Reduced syncytin-1 expression in choriocarcinoma BeWo cells activates the calpain1-AIF-mediated apoptosis, implication for preeclampsia. Cell Mol Life Sci 71(16):3151–3164.  https://doi.org/10.1007/s00018-013-1533-8 CrossRefGoogle Scholar
  17. 17.
    Toufaily C, Lokossou AG, Vargas A, Rassart E, Barbeau B (2015) A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model. PLoS ONE 10(3):e0121468.  https://doi.org/10.1371/journal.pone.0121468 CrossRefGoogle Scholar
  18. 18.
    Melo ASO, Chimelli L, Tanuri A (2017) Congenital zika virus infection: beyond neonatal microcephaly-reply. JAMA Neurol 74(5):610–611.  https://doi.org/10.1001/jamaneurol.2017.0051 CrossRefGoogle Scholar
  19. 19.
    Pham VH, Nguyen TV, Nguyen TT, Dang LD, Hoang NH, Nguyen TV, Abe K (2013) Rubella epidemic in Vietnam: characteristic of rubella virus genes from pregnant women and their fetuses/newborns with congenital rubella syndrome. J Clin Virol 57(2):152–156.  https://doi.org/10.1016/j.jcv.2013.02.008 CrossRefGoogle Scholar
  20. 20.
    Bebell LM, Riley LE (2015) Ebola virus disease and Marburg disease in pregnancy: a review and management considerations for filovirus infection. Obstet Gynecol 125(6):1293–1298.  https://doi.org/10.1097/AOG.0000000000000853 CrossRefGoogle Scholar
  21. 21.
    Marinho PS, Cunha AJ, Amim Junior J, Prata-Barbosa A (2017) A review of selected Arboviruses during pregnancy. Matern Health Neonatol Perinatol 3:17.  https://doi.org/10.1186/s40748-017-0054-0 CrossRefGoogle Scholar
  22. 22.
    Leon-Juarez M, Martinez-Castillo M, Gonzalez-Garcia LD, Helguera-Repetto AC, Zaga-Clavellina V, Garcia-Cordero J, Flores-Pliego A, Herrera-Salazar A, Vazquez-Martinez ER, Reyes-Munoz E (2017) Cellular and molecular mechanisms of viral infection in the human placenta. Pathog Dis.  https://doi.org/10.1093/femspd/ftx093 Google Scholar
  23. 23.
    Polack FP (2018) Respiratory syncytial virus during pregnancy. Clin Infect Dis 66(11):1666–1667.  https://doi.org/10.1093/cid/cix1091 CrossRefGoogle Scholar
  24. 24.
    Manti S, Cuppari C, Lanzafame A, Salpietro C, Betta P, Leonardi S, Perez MK, Piedimonte G (2017) Detection of respiratory syncytial virus (RSV) at birth in a newborn with respiratory distress. Pediatr Pulmonol 52(10):E81–E84.  https://doi.org/10.1002/ppul.23775 CrossRefGoogle Scholar
  25. 25.
    Piedimonte G, Perez MK (2014) Alternative mechanisms for respiratory syncytial virus (RSV) infection and persistence: could RSV be transmitted through the placenta and persist into developing fetal lungs? Curr Opin Pharmacol 16:82–88.  https://doi.org/10.1016/j.coph.2014.03.008 CrossRefGoogle Scholar
  26. 26.
    Ross AL, Cannou C, Barre-Sinoussi F, Menu E (2009) Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells. Retrovirology 6:46.  https://doi.org/10.1186/1742-4690-6-46 CrossRefGoogle Scholar
  27. 27.
    Delorme-Axford E, Sadovsky Y, Coyne CB (2013) Lipid raft- and SRC family kinase-dependent entry of coxsackievirus B into human placental trophoblasts. J Virol 87(15):8569–8581.  https://doi.org/10.1128/JVI.00708-13 CrossRefGoogle Scholar
  28. 28.
    Koi H, Zhang J, Makrigiannakis A, Getsios S, MacCalman CD, Strauss JF 3rd, Parry S (2002) Syncytiotrophoblast is a barrier to maternal-fetal transmission of herpes simplex virus. Biol Reprod 67(5):1572–1579CrossRefGoogle Scholar
  29. 29.
    Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques ET Jr, Cherry S, Sadovsky Y, Coyne CB (2016) Type III interferons produced by human placental trophoblasts confer protection against zika virus infection. Cell Host Microbe 19(5):705–712.  https://doi.org/10.1016/j.chom.2016.03.008 CrossRefGoogle Scholar
  30. 30.
    Chan JF, Yip CC, Tsang JO, Tee KM, Cai JP, Chik KK, Zhu Z, Chan CC, Choi GK, Sridhar S, Zhang AJ, Lu G, Chiu K, Lo AC, Tsao SW, Kok KH, Jin DY, Chan KH, Yuen KY (2016) Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs. Emerg Microbes Infect 5:e93.  https://doi.org/10.1038/emi.2016.99 Google Scholar
  31. 31.
    Yuan X, Hu T, He H, Qiu H, Wu X, Chen J, Wang M, Chen C, Huang S (2018) Respiratory syncytial virus prolifically infects N2a neuronal cells, leading to TLR4 and nucleolin protein modulations and RSV F protein co-localization with TLR4 and nucleolin. J Biomed Sci 25(1):13.  https://doi.org/10.1186/s12929-018-0416-6 CrossRefGoogle Scholar
  32. 32.
    Cao B, Diamond MS, Mysorekar IU (2017) Maternal-fetal transmission of zika virus: routes and signals for infection. J Interferon Cytokine Res 37(7):287–294.  https://doi.org/10.1089/jir.2017.0011 CrossRefGoogle Scholar
  33. 33.
    Lindholm K, O’Keefe M (2018) Placental cytomegalovirus infection. Arch Pathol Lab Med.  https://doi.org/10.5858/arpa.2017-0421-RS Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • M. A. Velázquez-Cervantes
    • 1
  • M. Martínez-Castillo
    • 1
  • L. D. González-García
    • 1
  • T. A. Vargas-Pavía
    • 1
  • M. G. Martínez-Salazar
    • 1
  • I. Mancilla-Herrera
    • 2
  • G. León-Reyes
    • 1
  • J. García-Cordero
    • 3
  • A. C. Helguera-Repetto
    • 1
  • M. León-Juárez
    • 1
    Email author
  1. 1.Departamento de InmunobioquímicaInstituto Nacional de Perinatología Isidro Espinosa de los ReyesMexico CityMexico
  2. 2.Departamento de Infectología e InmunologíaInstituto Nacional de Perinatología Isidro Espinosa de los ReyesMexico CityMexico
  3. 3.Departamento de Biomedicina MolecularCentro de Investigación y Estudios Avanzados del I.P.NMexico CityMexico

Personalised recommendations