Skip to main content

Advertisement

SpringerLink
Log in

Zika virus infection during pregnancy and vertical transmission: case reports and peptide-specific cell-mediated immune responses

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Zika virus (ZIKV) infection in pregnant women is associated with birth defects, which are more prevalent and severe the earlier in pregnancy the infection occurs. Pregnant women at risk of possible ZIKV exposure (n = 154) were screened using ELISA for ZIKV IgM and IgG. Nine of 154 (5.84%) pregnant women who underwent screening exhibited positive ZIKV serology. Of these, two maternal infections were confirmed by real-time RT-PCR and five were considered probable, but only three of those were retained for further analysis based on strict diagnostic criteria. Plaque reduction neutralization tests (PRNT) confirmed ZIKV infection in nine cases (5.84%). Two cases of vertical ZIKV transmission were confirmed by PCR. One infant showed no signs of congenital ZIKV syndrome and had a normal developmental profile despite first-trimester maternal infection. In the second case, pregnancy was terminated. Production of interferon γ (IFN-γ) by peripheral blood mononuclear cells obtained from pregnant women and umbilical cord blood was measured using enzyme-linked immunospot assay (ELISpot) after stimulation with panels of synthetic peptides derived from the sequence of ZIKV proteins. This analysis revealed that, among all peptide pools tested, those derived from the ZIKV envelope protein generated the strongest IFN-γ response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Experimental data is available from the corresponding author upon request.

References

  1. Gulland A (2016) Zika virus is a global public health emergency, declares WHO. BMJ 352:i657. https://doi.org/10.1136/bmj.i657

    Article  PubMed  Google Scholar 

  2. Johansson MA, Mier-y-Teran-Romero L, Reefhuis J, Gilboa SM, Hills SL (2016) Zika and the risk of microcephaly. N Engl J Med 375:1–4. https://doi.org/10.1056/NEJMp1605367

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR (2016) Zika virus and birth defects — reviewing the evidence for causality. N Engl J Med 374:1981–1987. https://doi.org/10.1056/NEJMsr1604338

    Article  CAS  PubMed  Google Scholar 

  4. Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, Fonseca EB, Ribeiro EM, Ventura LO, Neto NN, Arena JF, Rasmussen SA (2017) Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 171:288–295. https://doi.org/10.1001/jamapediatrics.2016.3982

    Article  PubMed  PubMed Central  Google Scholar 

  5. Reynolds MR, Jones AM, Petersen EE, Lee EH, Rice ME, Bingham A, Ellington SR, Evert N, Reagan-Steiner S, Oduyebo T, Brown CM, Martin S, Ahmad N, Bhatnagar J, Macdonald J, Gould C, Fine AD, Polen KD, Lake-Burger H, Hillard CL, Hall N, Yazdy MM, Slaughter K, Sommer JN, Adamski A, Raycraft M, Fleck-Derderian S, Gupta J, Newsome K, Baez-Santiago M, Slavinski S, White JL, Moore CA, Shapiro-Mendoza CK, Petersen L, Boyle C, Jamieson DJ, Meaney-Delman D, Honein MA; U.S. Zika Pregnancy Registry Collaboration (2017) Vital signs: Update on Zika virus-associated birth defects and evaluation of all U.S. infants with congenital Zika virus exposure-U.S. Zika Pregnancy Registry, 2016. MMWR Morb Mortal Wkly Rep 66:366-373. https://doi.org/10.15585/mmwr.mm6613e1

  6. Saad T, PennaeCosta AA, de Góes FV, de Freitas M, de Almeida JV, de Santa Ignêz LJ, Amancio AP, Alvim RJ, Antunes Kramberger LA (2018) Neurological manifestations of congenital Zika virus infection. Childs Nerv Syst 34:73–78. https://doi.org/10.1007/s00381-017-3634-4

    Article  PubMed  Google Scholar 

  7. Collier AY, Borducchi EN, Chandrashekar A, Moseley E, Peter L, Teodoro NS, Nkolola J, Abbink P, Barouch DH (2020) Sustained maternal antibody and cellular immune responses in pregnant women infected with Zika virus and mother to infant transfer of Zika-specific antibodies. Am J Reprod Immunol 84:e13288. https://doi.org/10.1111/aji.13288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Oliveira DB, Almeida FJ, Durigon EL, Mendes ÉA, Braconi CT, Marchetti I, Andreata-Santos R, Cunha MP, Alves RP, Pereira LR, Melo SR, Neto DF, Mesquita FS, Araujo DB, Favoretto SR, Sáfadi MA, Ferreira LC, Zanotto PM, Botosso VF, Berezin EN (2016) Prolonged shedding of Zika virus associated with congenital infection. N Engl J Med 375:1202–1204. https://doi.org/10.1056/NEJMc1607583

    Article  PubMed  Google Scholar 

  9. Moreira-Soto A, Sarno M, Pedroso C, Netto EM, Rockstroh A, Luz E, Feldmann M, Fischer C, Bastos FA, Kümmerer BM, de Lamballerie X, Drosten C, Ulbert S, Brites C, Drexler JF (2017) Evidence for congenital Zika virus infection from neutralizing antibody titers in maternal sera, Northeastern Brazil. J Infect Dis 216:1501–1504. https://doi.org/10.1093/infdis/jix539

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kakkar F, Boucoiran I (2019) The Women and Children’s Infectious Diseases Center: An integrated approach to congenital infectious diseases. Clin Invest Med 41:E211–E212. https://doi.org/10.25011/cim.v41i4.32223

  11. World Health Organization (2016) Laboratory testing for Zika virus infection: interim guidance. World Health Organization. https://apps.who.int/iris/handle/10665/204671 (Accessed September 11, 2023)

  12. Laboratoire de Santé publique du Québec (2019) Mise à jour des recommandations pour le diagnostic de laboratoire de l’infection par le virus Zika (version 6). https://www.inspq.qc.ca/sites/default/files/lspq/lettre_annonce_zika_version6.pdf (Accessed September 11, 2023)

  13. Plourde AR, Bloch EM (2016) A literature review of Zika virus. Emerg Infect Dis 22:1185–1192. https://doi.org/10.3201/eid2207.151990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mendoza EJ, Makowski K, Barairo N, Holloway K, Dimitrova K, Sloan A, Vendramelli R, Ranadheera C, Safronetz D, Drebot MA, Wood H (2019) Establishment of a comprehensive and high throughput serological algorithm for Zika virus diagnostic testing. Diagn Microbiol Infect Dis 94:140–146. https://doi.org/10.1016/j.diagmicrobio.2019.01.004

    Article  CAS  PubMed  Google Scholar 

  15. Dimitrova K, Mendoza EJ, Mueller N, Wood H (2020) A plaque reduction neutralization test for the detection of ZIKV-specific antibodies. In: Kobinger G, Racine T (eds) Zika Virus. Methods in Molecular Biology, vol 2142. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0581-3_5

  16. 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 14:1232–1239. https://doi.org/10.3201/eid1408.080287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. World Health Organization (2022) Laboratory testing for Zika virus and dengue virus infections: interim guidance. World Health Organization. https://www.who.int/publications/i/item/WHO-ZIKV_DENV-LAB-2022.1 (Accessed September 11, 2023)

  18. Salem Fourati I, Grenier AJ, Jolette É, Merindol N, Ovetchkine P, Soudeyns H (2014) Development of an IFN-γ ELISpot assay to assess varicella-zoster virus-specific cell-mediated immunity following umbilical cord blood transplantation. J Vis Exp 89:51643. https://doi.org/10.3791/51643

    Article  CAS  Google Scholar 

  19. Hindle S, Brien MÈ, Pelletier F, Giguère F, Trudel MJ, Dal Soglio D, Kakkar F, Soudeyns H, Girard S, Boucoiran I (2023) Placenta analysis of Hofbauer cell profile according to the class of antiretroviral therapy used during pregnancy in people living with HIV. Placenta 139:120–126. https://doi.org/10.1016/j.placenta.2023.06.003

    Article  CAS  PubMed  Google Scholar 

  20. Khong TY, Mooney EE, Ariel I, Balmus NC, Boyd TK, Brundler MA, Derricott H, Evans MJ, Faye-Petersen OM, Gillan JE, Heazell AE, Heller DS, Jacques SM, Keating S, Kelehan P, Maes A, McKay EM, Morgan TK, Nikkels PG, Parks WT, Redline RW, Scheimberg I, Schoots MH, Sebire NJ, Timmer A, Turowski G, van der Voorn JP, van Lijnschoten I, Gordijn SJ (2016) Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med 140:698–713. https://doi.org/10.5858/arpa.2015-0225-CC

    Article  PubMed  Google Scholar 

  21. Baud D, Gubler DJ, Schaub B, Lanteri MC, Musso D (2017) An update on Zika virus infection. Lancet 390:2099–2109. https://doi.org/10.1016/S0140-6736(17)31450-2

    Article  PubMed  Google Scholar 

  22. Tonnerre P, Melgaço JG, Torres-Cornejo A, Pinto MA, Yue C, Blümel J, de Sousa PSF, de Mello VDM, Moran J, de Filippis AMB, Wolski D, Grifoni A, Sette A, Barouch DH, Hoogeveen RC, Baylis SA, Lauer GM, Lewis-Ximenez LL (2020) Evolution of the innate and adaptive immune response in women with acute Zika virus infection. Nat Microbiol 5:76–83. https://doi.org/10.1038/s41564-019-0618-z

    Article  CAS  PubMed  Google Scholar 

  23. Chaudhary V, Yuen KS, Chan JF, Chan CP, Wang PH, Cai JP, Zhang S, Liang M, Kok KH, Chan CP, Yuen KY, Jin DY (2017) Selective activation of type II interferon signaling by Zika virus NS5 protein. J Virol 91:e00163-e217. https://doi.org/10.1128/JVI.00163-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cimini E, Castilletti C, Sacchi A, Casetti R, Bordoni V, Romanelli A, Turchi F, Martini F, Tumino N, Nicastri E, Corpolongo A, Di Caro A, Kobinger G, Zumla A, Capobianchi MR, Ippolito G, Agrati C (2017) Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells. Sci Rep 7:6313. https://doi.org/10.1038/s41598-017-06536-x

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  25. Ades AE, Soriano-Arandes A, Alarcon A, Bonfante F, Thorne C, Peckham CS, Giaquinto C (2021) Vertical transmission of Zika virus and its outcomes: a Bayesian synthesis of prospective studies. Lancet Infect Dis 21:537–545. https://doi.org/10.1016/S1473-3099(20)30432-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pomar L, Lambert V, Madec Y, Vouga M, Pomar C, Matheus S, Fontanet A, Panchaud A, Carles G, Baud D (2020) Placental infection by Zika virus in French Guiana. Ultrasound Obstet Gynecol 56:740–748. https://doi.org/10.1002/uog.21936

    Article  CAS  PubMed  Google Scholar 

  27. Pomar L, Vouga M, Lambert V, Pomar C, Hcini N, Jolivet A, Benoist G, Rousset D, Matheus S, Malinger G, Panchaud A, Carles G, Baud D (2018) Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana. BMJ 363:k4431. https://doi.org/10.1136/bmj.k4431

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hcini N, Kugbe Y, Rafalimanana ZHL, Lambert V, Mathieu M, Carles G, Baud D, Panchaud A, Pomar L (2021) Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life. Nat Commun 12:3270. https://doi.org/10.1038/s41467-021-23468-3

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  29. Lemos de Carvalho A, Brites C, Taguchi TB, Pinho SF, Campos G, Lucena R (2018) Congenital Zika virus infection with normal neurodevelopmental outcome. Brazil Emerg Infect Dis 24:2128–2130. https://doi.org/10.3201/eid2411.180883

    Article  PubMed  Google Scholar 

  30. Paquin-Proulx D, Leal FE, Terrassani Silveira CG, Maestri A, Brockmeyer C, Kitchen SM, Cabido VD, Kallas EG, Nixon DF (2017) T-cell responses in individuals infected with Zika virus and in those vaccinated against Dengue virus. Pathog Immun 2:274-292. https://doi.org/10.20411/pai.v2i2

  31. Zavattoni M, Rovida F, Percivalle E, Cassaniti I, Sarasini A, Arossa A, Tassis B, Bollani L, Lombardi G, Orcesi S, Baldanti F (2019) Zika virus infection in pregnancy: Advanced diagnostic approaches in Dengue-naive and Dengue-experienced pregnant women and possible implication for cross-reactivity and cross-protection. Microorganisms 8:56. https://doi.org/10.3390/microorganisms8010056

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wen J, Elong Ngono A, Regla-Nava JA, Kim K, Gorman MJ, Diamond MS, Shresta S (2017) Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge. Nat Commun 8:1459. https://doi.org/10.1038/s41467-017-01669-z

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  33. Masmejan S, Musso D, Vouga M, Pomar L, Dashraath P, Stojanov M, Panchaud A, Baud D (2020) Zika virus. Pathogens 9:898. https://doi.org/10.3390/pathogens9110898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Martine Caty and Silvie Valois for expert technical assistance.

Author information

Authors and Affiliations

  1. Centre d’infectiologie mère-enfant (CIME), Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Room 7. 9. 61, Montreal, Quebec, H3T 1C5, Canada

    Stéphanie Hindle, Hugo Soudeyns & Isabelle Boucoiran

  2. Faculty of Medicine, Department of Pharmacology and Physiology, Université de Montréal, Montreal, Quebec, Canada

    Stéphanie Hindle

  3. Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, Montreal, Quebec, Canada

    Agnès Depatureaux, Samuel Fortin-Dion, Hinatea Dieumegard & Hugo Soudeyns

  4. Faculty of Medicine, Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada

    Agnès Depatureaux, Samuel Fortin-Dion, Hinatea Dieumegard, Christian Renaud & Hugo Soudeyns

  5. Department of Microbiology, CHU Sainte-Justine, Montreal, Quebec, Canada

    Christian Renaud

  6. Laboratoire de santé publique du Québec, Sainte-Anne-de-Bellevue, Quebec, Canada

    Christian Therrien

  7. Departement of Pathology, CHU Sainte-Justine, Montreal, Quebec, Canada

    Catherine Fallet-Bianco

  8. Faculty of Medicine, Department of Pathology and Cell Biology, Université de Montréal, Montreal, Quebec, Canada

    Catherine Fallet-Bianco

  9. Infectious Diseases Service, CHU Sainte-Justine, Montreal, Quebec, Canada

    Valérie Lamarre

  10. Faculty of Medicine, Department of Pediatrics, Université de Montréal, Montreal, Quebec, Canada

    Valérie Lamarre & Hugo Soudeyns

  11. Obstetrics and Gynecology Service, CHU Sainte-Justine, Montreal, Quebec, Canada

    Isabelle Boucoiran

  12. Faculty of Medicine, Department of Obstetrics and Gynecology, Université de Montréal, Montreal, Quebec, Canada

    Isabelle Boucoiran

Authors
  1. Stéphanie Hindle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agnès Depatureaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samuel Fortin-Dion
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hinatea Dieumegard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Renaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christian Therrien
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Catherine Fallet-Bianco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Valérie Lamarre
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hugo Soudeyns
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Isabelle Boucoiran
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.S. and I.B. designed research. A.D., M.T.H., H.D., C.R., C.F.B., and C.T. performed research. NL, MB, PS, and JK provided key reagents and technologies. S.H., A.D., C.R., C.T., C.F.B., H.S., and I.B. analyzed the data. S.H., A.D., H.S., and I.B. wrote the manuscript.

Corresponding author

Correspondence to Hugo Soudeyns.

Ethics declarations

Conflict of interest

H.S. was the recipient of an infrastructure grant from Réseau SIDA et maladies infectieuses of the Fonds de la recherche du Québec-santé (FRQS). I.B. is the holder of a Junior 2 Career Scholarship from FRQS. The authors have no relevant financial or non-financial interests to disclose.

Compliance with ethical standards

All participants provided written informed consent. The study was approved by the Ethics Review Board of CHU Sainte-Justine, where the study was conducted.

Additional information

Handling Editor: Patricia Aguilar.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hindle, S., Depatureaux, A., Fortin-Dion, S. et al. Zika virus infection during pregnancy and vertical transmission: case reports and peptide-specific cell-mediated immune responses. Arch Virol 169, 32 (2024). https://doi.org/10.1007/s00705-023-05952-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00705-023-05952-x

Search

Navigation