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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
RESUMEN

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.

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Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
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Cell Freezing Medium-DMSO 1×, sterile-filtered, suitable for cell culture
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Penicillin-Streptomycin, Solution stabilized, with 10,000 units penicillin and 10 mg streptomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture
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Phosphate buffered saline, pH 7.2 (25 °C)
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Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture