Multiplexed Biomarker Panels Discriminate Zika and Dengue Virus Infection in Humans

Guang Song,Hee-Sool Rho,Jianbo Pan,Pedro Ramos,Ki-Jun Yoon,Freddy A Medina,Emily M Lee,Daniel Eichinger,Guo-Li Ming,Jorge L Muñoz-Jordan,Hengli Tang,Ignacio Pino,Hongjun Song,Jiang Qian,Heng Zhu

doi:10.1074/mcp.ra117.000310

Abstract

Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas. We have developed a ZIKV/DENV protein array and tested it with serum samples collected from ZIKV- and DENV-infected patients and healthy subjects in Puerto Rico. Our analyses reveal a biomarker panel that are capable of discriminating ZIKV and DENV infections with high accuracy, including Capsid protein from African ZIKV strain MR766, and other 5 pair of proteins (NS1, NS2A, NS3, NS4B and NS5) from ZIKV and DENV respectively. Both sensitivity and specificity of the test for ZIKV from DENV are around 90%. We propose that the ZIKV/DENV protein array will be used in future studies to discriminate patients infected with ZIKV from DENV.

Highlights

From the ‡Department of Pharmacology & Molecular Sciences; Johns Hopkins School of Medicine, Baltimore, Maryland 21205; §Department of Ophthalmology; Johns Hopkins School of Medicine, Baltimore, Maryland 21205; ¶CDI Laboratories, Inc
We propose that the Zika virus (ZIKV)/dengue virus (DENV) protein array will be used in future studies to discriminate patients infected with ZIKV from DENV
A DENV protein microarray were fabricated through gene synthesis and successfully applied to discriminate patients infected by DENV from other related pathogens, or uninfected patients [11], suggesting a protein array containing proteomes of ZIKV and DENV would be an effective method to differentiate patients infected by ZIKV or DENV

Summary

Introduction

From the ‡Department of Pharmacology & Molecular Sciences; Johns Hopkins School of Medicine, Baltimore, Maryland 21205; §Department of Ophthalmology; Johns Hopkins School of Medicine, Baltimore, Maryland 21205; ¶CDI Laboratories, Inc. Analyses reveal a biomarker panel that are capable of discriminating ZIKV and DENV infections with high accuracy, including Capsid protein from African ZIKV strain MR766, and other 5 pair of proteins (NS1, NS2A, NS3, NS4B and NS5) from ZIKV and DENV respectively Both sensitivity and specificity of the test for ZIKV from DENV are around 90%. ZIKV infection is known to be a cause of microcephaly and severe brain abnormalities and has been linked to other birth defects (https://www.cdc.gov/zika/pdfs/zikakey-messages.pdf) It has become one of the greatest concerns for pregnant women, who can pass ZIKV to their developing fetus if infected during pregnancy [2]. Biomarker for Zika and Dengue Virus Infection atic pregnant women, differentiating these two diseases requires specific serology-based diagnostic methods, which is challenging because of immunologic cross-reactivity among the flaviviruses [3]. A DENV protein microarray were fabricated through gene synthesis and successfully applied to discriminate patients infected by DENV from other related pathogens, or uninfected patients [11], suggesting a protein array containing proteomes of ZIKV and DENV would be an effective method to differentiate patients infected by ZIKV or DENV

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