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Innate immune response in patients with acute Zika virus infection

  • Marcelo Henrique Matias da Silva
  • Raiza Nara Cunha Moises
  • Brenda Elen Bizerra Alves
  • Hannaly Wana Bezerra Pereira
  • Anne Aline Pereira de Paiva
  • Ingryd Câmara Morais
  • Yasmim Mesquita Nascimento
  • Joelma Dantas Monteiro
  • Janeusa Trindade de Souto
  • Manuela Sales Lima Nascimento
  • Josélio Maria Galvão de Araújo
  • Paulo Marcos Matta da GuedesEmail author
  • José Veríssimo FernandesEmail author
Original Investigation

Abstract

Innate immunity receptors (Toll-like receptors/TLRs and RIG-like receptors/RLRs) are important for the initial recognition of Zika virus (ZIKV), modulation of protective immune response, and IFN-α and IFN-β production. Immunological mechanisms involved in protection or pathology during ZIKV infection have not yet been determined. In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and retinoic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88, Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β/TRIF), and cytokines (IL-6, IL-12, TNF-α, IFN-α, IFN-β, and IFN-γ) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-α, IFN-β, and IFN-γ when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression compared to IFN-α and IFN-β. Moreover, viral load is positively correlated with TLR8, RIG-1, MDA-5, IFN-α, and IFN-β. On the other hand, patients infected by ZIKV showed reduced expression of RIG-1, TLR8, Myd88, and TNF-α molecules, which are also involved in antiviral immunity. Similar expressions of TLR7, TLR9, MDA-5, TRIF, IL-6, and IL-12 were observed between the group of patients infected with ZIKV and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by ZIKV in patients induces the high mRNA expression of TLR3 correlated to high expression of IFN-γ, IFN-α, and IFN-β, even though the high viral load is correlated to high expression of TLR8, RIG-1, MDA-5, IFN-α, and IFN-β in ZIKV patients.

Keywords

Zika virus Patient Innate immune receptors Toll-like receptors (TLRs) RIG-like receptors (RLRs) Cytokines 

Notes

Acknowledgements

This work was supported by the National Council for Scientific and Technological Development (MEC/MCTI/CAPES/CNPq/FAPS-PVE Grant no. 400328/2014-3 and MCTI/CNPq/Universal Grant no. 404904/2016-5). Post-graduation research fellows are supported by University Faculty Advanced Studies Coordination Unit (CAPES). The author PMMG acknowledges the CNPq for the research productivity fellowship.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Marcelo Henrique Matias da Silva
    • 1
  • Raiza Nara Cunha Moises
    • 2
  • Brenda Elen Bizerra Alves
    • 1
    • 2
    • 3
  • Hannaly Wana Bezerra Pereira
    • 1
    • 2
    • 3
  • Anne Aline Pereira de Paiva
    • 2
    • 3
  • Ingryd Câmara Morais
    • 3
  • Yasmim Mesquita Nascimento
    • 2
    • 3
  • Joelma Dantas Monteiro
    • 2
    • 3
  • Janeusa Trindade de Souto
    • 1
    • 2
  • Manuela Sales Lima Nascimento
    • 4
  • Josélio Maria Galvão de Araújo
    • 1
    • 2
    • 3
  • Paulo Marcos Matta da Guedes
    • 1
    • 2
    Email author
  • José Veríssimo Fernandes
    • 1
    • 2
    Email author
  1. 1.Graduate Program in Parasitary Biology, Department of Microbiology and ParasitologyFederal University of Rio Grande do NorteNatalBrazil
  2. 2.Department of Microbiology and ParasitologyFederal University of Rio Grande do NorteNatalBrazil
  3. 3.Laboratory of Virology, Institute of Tropical MedicineFederal University of Rio Grande do NorteNatalBrazil
  4. 4.Edmond and Lily Safra International Institute of Neuroscience (ELS-IIN), Santos Dumont InstituteMacaíbaBrazil

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