Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice

Zika virus (ZIKV) is a significant global health threat due to its potential for rapid emergence and association with severe congenital malformations during infection in pregnancy. Despite the urgent need, accurate diagnosis of ZIKV infection is still a major hurdle that must be overcome. Contributing to the inaccuracy of most serologically-based diagnostic assays for ZIKV, is the substantial geographic and antigenic overlap with other flaviviruses, including the four serotypes of dengue virus (DENV). Within this study, we have utilized a novel T cell receptor (TCR) sequencing platform to distinguish between ZIKV and DENV infections. Using high-throughput TCR sequencing of lymphocytes isolated from DENV and ZIKV infected mice, we were able to develop an algorithm which could identify virus-associated TCR sequences uniquely associated with either a prior ZIKV or DENV infection in mice. Using this algorithm, we were then able to separate mice that had been exposed to ZIKV or DENV infection with 97% accuracy. Overall this study serves as a proof-of-principle that T cell receptor sequencing can be used as a diagnostic tool capable of distinguishing between closely related viruses. Our results demonstrate the potential for this innovative platform to be used to accurately diagnose Zika virus infection and potentially the next emerging pathogen(s).

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Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor–Mediated T-Cell Function by an RNA-Based Mechanism

The Journal of Infectious Diseases ◽

10.1093/infdis/jix462 ◽

2017 ◽

Vol 216 (9) ◽

pp. 1164-1175 ◽

Cited By ~ 5

Author(s):

James H McLinden ◽

Nirjal Bhattarai ◽

Jack T Stapleton ◽

Qing Chang ◽

Thomas M Kaufman ◽

...

Keyword(s):

T Cell ◽

Dengue Virus ◽

T Cell Receptor ◽

Yellow Fever ◽

Zika Virus ◽

Cell Function ◽

Yellow Fever Virus ◽

Cell Receptor ◽

Fever Virus ◽

T Cell Function

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T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

Pathogens and Immunity ◽

10.20411/pai.v2i2.188 ◽

2017 ◽

Vol 2 (2) ◽

pp. 274 ◽

Cited By ~ 13

Author(s):

Dominic Paquin-Proulx ◽

Fabio E. Leal ◽

Cassia G. Terrassani Silveira ◽

Alvino Maestri ◽

Claudia Brockmeyer ◽

...

Keyword(s):

T Cell ◽

Dengue Virus ◽

Zika Virus ◽

Cell Response ◽

Cell Epitope ◽

Denv Infection ◽

Cross Reactivity ◽

T Cell Response ◽

Cd4 T Cell ◽

T Cell Epitopes

Background: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection.Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT.Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects.Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

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