Multiplexed Biomarker Panels Discriminate Zika and Dengue Virus Infection in Humans

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.

Pathophysiology and Mechanisms of Zika Virus Infection in the Nervous System

“…Protein biomarkers are another potential target for increasing the accuracy and availability of diagnostics to differentiate among closely related viruses. A recent study showed that the protein array tested was approximately 90% effective in distinguishing between ZIKV and dengue virus using serum from infected patients and uninfected controls (Song et al 2018). Moving toward field-based diagnostics, one group recently described the development of a paper microfluidic chip that relies on reverse transcription loop-mediated isothermal amplification and imaging that could be performed by a smartphone (Kaarj et al 2018).…”

An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication

“…Gateway cloning and protein expression were performed using the method as our previous publication [58]. In short, primer sets with the attB1 or attB2 sequences at the 5´and 3'-ends (Table S1) shuttled into the yeast expression vector pEGH-A to carry out the protein expression.…”

High-resolution proteomics identifies potential new markers of Zika and dengue infections

“…the concentration of serum albumin is an order of magnitude larger than that of other proteins. Even most advanced proteomics studies struggle to identify more than a few hundred proteins 8,9 . The problem is exacerbated in studies that struggle with obtaining sufficient protein sample or are collected under suboptimal conditions.…”