Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection
Daniela Michlmayra, Eun‐Young Kimb, Adeeb H Rahmanc d, Rohit R. Raghunathane, Seunghee Kim‐Schulzec f, Yan Cheb, Selim Kalaycıd g, Zeynep Hulya Gumusd g, Guillermina M. Kuanh i, Ángel Balmasedai j, Andrew Kasarskisd g, Steven M. Wolinsky
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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.
TL;DRInterestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika, and this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource. (Semantic Scholar)