Abstract
Zika virus (ZIKV) is a mosquito-borne pathogen causing a febrile illness with arthralgia, conjunctivitis and rash. The complications include Guillain-Barré syndrome, congenital brain and other abnormalities and miscarriage. The serodiagnosis of ZIKV infection is hampered by cross-reactivity with other members of the Flavivirus family, notably dengue (DENV). This report describes a novel serological platform for the diagnosis of ZIKV infection. The approach utilizes time-resolved Förster resonance energy transfer (TR-FRET) elicited by two chromophore-labeled proteins (a ZIKV antigen and a super-antigen) simultaneously binding to a given antibody molecule. The antigen used in the assay is ZIKV non-structural protein 1 (NS1) and the super-antigen is bacterial protein L. Three assay variants were developed: the first measuring all anti-ZIKV-NS1 antibodies (LFRET), the second measuring IgM and IgA (acute-LFRET) and the third measuring IgG (immunity-LFRET). The assays were evaluated with a panel of samples from clinical ZIKV cases in travelers (n = 25) and seronegative (n = 24) samples. DENV (n = 38), yellow fever (n = 16) and tick-borne-encephalitis (n = 20) seropositive samples were examined for assessment of flavivirus cross-reactivity. The diagnostic sensitivities of the respective LFRET assays were 92%, 100% and 83%, and the diagnostic specificities 88%, 95% and 100% for LFRET, acute-LFRET and immunity-LFRET. Furthermore, we evaluated the assays against a widely-used commercial ELISA. In conclusion, the new FRET-based serological approaches based on NS1 protein are applicable to diagnosing zika virus infections in travelers and differentiating them from other flavivirus infections.
Highlights
The rapid and accurate diagnosis of the causative agent is the first step in effective management of infectious disease
We demonstrate a method for Zika virus (ZIKV) serodiagnosis using non-structural protein 1 (NS1) labelled with chelated Eu as the donor and protein L labelled with AlexaFluor 647 as the acceptor
Since flavivirus serodiagnostics are known to suffer from inter-species cross-reactivity, we analyzed a panel of well-characterized sera representing acute infections with dengue virus (DENV) (n = 38) and tick-borne encephalitis virus (TBEV) (n = 20) and yellow fever virus (YFV) vaccinees (n = 16) as well as additional negative samples (n = 2) and cases of ZIKV (n = 10) with LFRET
Summary
The rapid and accurate diagnosis of the causative agent is the first step in effective management of infectious disease. Many agents have similar symptoms and without clear laboratory. Immunoassay for serodiagnosis of Zika virus infection. Finland (www.aka.fi), the Finnish Medical Society of Finland (https://laaketieteensaatio.fi/) and the Sigrid Juselius Foundation (https://sigridjuselius.fi/ ). Several of the researches had individual grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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