Innate immune response in patients with acute Zika virus infection
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.
KeywordsZika virus Patient Innate immune receptors Toll-like receptors (TLRs) RIG-like receptors (RLRs) Cytokines
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.
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Conflict of interest
The authors have no conflicts of interest to declare.
- 22.Pierson T, Fremont D, Kuhn R, Diamond M (2013) Structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development. Cell Host Microbe 17:148–159. https://doi.org/10.1007/s10461-012-0143-z.Provider-patient Google Scholar
- 32.Lubick KJ, Robertson S, McNally K et al (2015) Flavivirus antagonism of type I interferon signaling reveals prolidase as a regulator of IFNAR1 surface expression. Cell Host Microbe 18:61–74. https://doi.org/10.1097/RCT.0000000000000239.Texture CrossRefGoogle Scholar
- 34.Ngono AE, Vizcarra EA, Tang W et al (2017) Mapping and role of the CD8+ T cell response during primary Zika virus infection in mice. Cell Host Microbe 21:35–46. https://doi.org/10.1007/s10549-015-3663-1.Progestin CrossRefGoogle Scholar
- 40.Ornelas AM, Pezzuto P, Silveira PP, Melo FO, Ferreira TA, Oliveira-Szejnfeld PS, Leal JI, Amorim MM, Hamilton S, Rawlinson WD, Cardoso CC, Nixon DF, Tanuri A, Melo AS, Aguiar RS (2017) Immuneactivation in amniotic fluid from Zika virus-associated microcephaly. Ann Neurol 81(1):152–156CrossRefGoogle Scholar
- 41.Simoni M, Jurado KA, Abrahams VM et al (2017) Zika virus infection of Hofbauer cells. Am J ReprodImmunol 77:1–8Google Scholar