Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections

ABSTRACTThe recent outbreaks of Zika virus (ZIKV) in flavivirus-endemic regions highlight the need for sensitive and specific serological tests. Previously we and others reported key fusion loop (FL) residues and/or BC loop (BCL) residues on dengue virus (DENV) envelope protein recognized by flavivi...

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Main Authors: Wen-Yang Tsai, Kaitlin Driesse, Jih-Jin Tsai, Szu-Chia Hsieh, Robert Sznajder Granat, Olivia Jenkins, Gwong-Jen Chang, Wei-Kung Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1797540
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author Wen-Yang Tsai
Kaitlin Driesse
Jih-Jin Tsai
Szu-Chia Hsieh
Robert Sznajder Granat
Olivia Jenkins
Gwong-Jen Chang
Wei-Kung Wang
author_facet Wen-Yang Tsai
Kaitlin Driesse
Jih-Jin Tsai
Szu-Chia Hsieh
Robert Sznajder Granat
Olivia Jenkins
Gwong-Jen Chang
Wei-Kung Wang
author_sort Wen-Yang Tsai
collection DOAJ
description ABSTRACTThe recent outbreaks of Zika virus (ZIKV) in flavivirus-endemic regions highlight the need for sensitive and specific serological tests. Previously we and others reported key fusion loop (FL) residues and/or BC loop (BCL) residues on dengue virus (DENV) envelope protein recognized by flavivirus cross-reactive human monoclonal antibodies and polyclonal sera. To improve ZIKV serodiagnosis, we employed wild type (WT) and FL or FL/BCL mutant virus-like particles (VLP) of ZIKV, DENV1 and West Nile virus (WNV) in enzyme linked immunosorbent assays (ELISA), and tested convalescent-phase serum or plasma samples from reverse-transcription PCR-confirmed cases with different ZIKV, DENV and WNV infections. For IgG ELISA, ZIKV WT-VLP had a sensitivity of 100% and specificity of 52.9%, which was improved to 83.3% by FL/BCL mutant VLP and 92.2% by the ratio of relative optical density of mutant to WT VLP. Similarly, DENV1 and WNV WT-VLP had a sensitivity/specificity of 100%/70.0% and 100%/56.3%, respectively; the specificity was improved to 93.3% and 83.0% by FL mutant VLP. For IgM ELISA, ZIKV, DENV1 and WNV WT-VLP had a specificity of 96.4%, 92.3% and 91.4%, respectively, for primary infection; the specificity was improved to 93.7–99.3% by FL or FL/BCL mutant VLP. An algorithm based on a combination of mutant and WT-VLP IgG ELISA is proposed to discriminate primary ZIKV, DENV and WNV infections as well as secondary DENV and ZIKV infection with previous DENV infections; this could be a powerful tool to better understand the seroprevalence and pathogenesis of ZIKV in regions where multiple flaviviruses co-circulate.
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spelling doaj.art-0ef5f509b30e44f79addc967bb32e8a42024-03-11T16:04:23ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01911722173210.1080/22221751.2020.1797540Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infectionsWen-Yang Tsai0Kaitlin Driesse1Jih-Jin Tsai2Szu-Chia Hsieh3Robert Sznajder Granat4Olivia Jenkins5Gwong-Jen Chang6Wei-Kung Wang7Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USADepartment of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USATropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USAFaculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USADivision of Vector-Borne Diseases, Center for Disease Control and Prevention, US Department of Health and Human Service, Fort Collins, CO, USADepartment of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USAABSTRACTThe recent outbreaks of Zika virus (ZIKV) in flavivirus-endemic regions highlight the need for sensitive and specific serological tests. Previously we and others reported key fusion loop (FL) residues and/or BC loop (BCL) residues on dengue virus (DENV) envelope protein recognized by flavivirus cross-reactive human monoclonal antibodies and polyclonal sera. To improve ZIKV serodiagnosis, we employed wild type (WT) and FL or FL/BCL mutant virus-like particles (VLP) of ZIKV, DENV1 and West Nile virus (WNV) in enzyme linked immunosorbent assays (ELISA), and tested convalescent-phase serum or plasma samples from reverse-transcription PCR-confirmed cases with different ZIKV, DENV and WNV infections. For IgG ELISA, ZIKV WT-VLP had a sensitivity of 100% and specificity of 52.9%, which was improved to 83.3% by FL/BCL mutant VLP and 92.2% by the ratio of relative optical density of mutant to WT VLP. Similarly, DENV1 and WNV WT-VLP had a sensitivity/specificity of 100%/70.0% and 100%/56.3%, respectively; the specificity was improved to 93.3% and 83.0% by FL mutant VLP. For IgM ELISA, ZIKV, DENV1 and WNV WT-VLP had a specificity of 96.4%, 92.3% and 91.4%, respectively, for primary infection; the specificity was improved to 93.7–99.3% by FL or FL/BCL mutant VLP. An algorithm based on a combination of mutant and WT-VLP IgG ELISA is proposed to discriminate primary ZIKV, DENV and WNV infections as well as secondary DENV and ZIKV infection with previous DENV infections; this could be a powerful tool to better understand the seroprevalence and pathogenesis of ZIKV in regions where multiple flaviviruses co-circulate.https://www.tandfonline.com/doi/10.1080/22221751.2020.1797540Zika virusflavivirusvirus-like particlesserodiagnosisfusion loop
spellingShingle Wen-Yang Tsai
Kaitlin Driesse
Jih-Jin Tsai
Szu-Chia Hsieh
Robert Sznajder Granat
Olivia Jenkins
Gwong-Jen Chang
Wei-Kung Wang
Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
Emerging Microbes and Infections
Zika virus
flavivirus
virus-like particles
serodiagnosis
fusion loop
title Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
title_full Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
title_fullStr Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
title_full_unstemmed Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
title_short Enzyme-linked immunosorbent assays using virus-like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
title_sort enzyme linked immunosorbent assays using virus like particles containing mutations of conserved residues on envelope protein can distinguish three flavivirus infections
topic Zika virus
flavivirus
virus-like particles
serodiagnosis
fusion loop
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1797540
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