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. Contributi...
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Online Access: | https://doi.org/10.1371/journal.pntd.0008896 |
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doaj-2e81b957e2684505a01fa72a697f58582021-03-03T08:32:40ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-12-011412e000889610.1371/journal.pntd.0008896Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice.Mariah HassertKyle J WolfAhmad RajehCourtney SchieboutStella G HoftTae-Hyuk AhnRichard J DiPaoloJames D BrienAmelia K PintoZika 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).https://doi.org/10.1371/journal.pntd.0008896 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mariah Hassert Kyle J Wolf Ahmad Rajeh Courtney Schiebout Stella G Hoft Tae-Hyuk Ahn Richard J DiPaolo James D Brien Amelia K Pinto |
spellingShingle |
Mariah Hassert Kyle J Wolf Ahmad Rajeh Courtney Schiebout Stella G Hoft Tae-Hyuk Ahn Richard J DiPaolo James D Brien Amelia K Pinto Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice. PLoS Neglected Tropical Diseases |
author_facet |
Mariah Hassert Kyle J Wolf Ahmad Rajeh Courtney Schiebout Stella G Hoft Tae-Hyuk Ahn Richard J DiPaolo James D Brien Amelia K Pinto |
author_sort |
Mariah Hassert |
title |
Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice. |
title_short |
Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice. |
title_full |
Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice. |
title_fullStr |
Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice. |
title_full_unstemmed |
Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice. |
title_sort |
diagnostic differentiation of zika and dengue virus exposure by analyzing t cell receptor sequences from peripheral blood of infected hla-a2 transgenic mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2020-12-01 |
description |
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). |
url |
https://doi.org/10.1371/journal.pntd.0008896 |
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