Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection.

Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection.

Cell reports (2020-04-30)

Daniela Michlmayr, Eun-Young Kim, Adeeb H Rahman, Rohit Raghunathan, Seunghee Kim-Schulze, Yan Che, Selim Kalayci, Zeynep H Gümüş, Guillermina Kuan, Angel Balmaseda, Andrew Kasarskis, Steven M Wolinsky, Mayte Suaréz-Fariñas, Eva Harris

PMID32348760

ABSTRACT

Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR-confirmed ZIKV infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. We analyze the samples via RNA sequencing (RNA-seq), CyTOF, and multiplex cytokine/chemokine Luminex to generate a comprehensive, innate immune profile during ZIKV infection. Immunophenotyping and analysis of cytokines/chemokines reveal that CD14+ monocytes play a key role during ZIKV infection. Further, we identify CD169 (Siglec-1) on CD14+ monocytes as a potential biomarker of acute ZIKV infection. Strikingly distinct transcriptomic and immunophenotypic signatures are observed at all three time points. Interestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika. Finally, this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource.

MATERIALS

Product Number

Brand

Product Description

P4333

Sigma-Aldrich

Penicillin-Streptomycin, Solution stabilized, with 10,000 units penicillin and 10 mg streptomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture

C6164

Sigma-Aldrich

Cell Freezing Medium-DMSO 1×, sterile-filtered, suitable for cell culture

252549

Sigma-Aldrich

Formaldehyde solution, ACS reagent, 37 wt. % in H₂O, contains 10-15% Methanol as stabilizer (to prevent polymerization)

HSTCMAG-28SK

Millipore

MILLIPLEX^® Human High Sensitivity T Cell Panel - Immunology Multiplex Assay, Simultaneous analyze low levels of cytokine and chemokine biomarker with the High Sensitivity Bead-Based Multiplex Assays using the Luminex technology, in human serum, plasma and cell culture samples.

IP10

Millipore

Protein G Plus/Protein A-Agarose, A mixture of Protein G PLUS and Protein A covalently conjugated to agarose. Useful for purification of IgG from biological fluids.

E6758

Sigma-Aldrich

Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture

P5119

Sigma-Aldrich

Phosphate buffered saline, pH 7.2 (25 °C)