Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection
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
Affiliations
Daniela Michlmayr
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
Eun-Young Kim
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Adeeb H. Rahman
Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Rohit Raghunathan
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Seunghee Kim-Schulze
Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Yan Che
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Selim Kalayci
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Zeynep H. Gümüş
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Guillermina Kuan
Centro de Salud Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua
Angel Balmaseda
Sustainable Sciences Institute, Managua, Nicaragua; Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua
Andrew Kasarskis
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Steven M. Wolinsky
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Mayte Suaréz-Fariñas
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Eva Harris
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA; Corresponding author
Summary: 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. : At three time points after Zika virus infection, Michlmayr et al. perform comprehensive immunoprofiling of pediatric cohort samples via RNA-seq, CyTOF, and Luminex cytokine/chemokine array, resulting in distinct temporal patterns of gene expression, cell profiles, and cytokines/chemokines. They show CD14+ monocytes play a central role, identify CD169 as a potential biomarker of acute ZIKV infection along with upregulation of CXCL10, and find no impact of prior dengue virus infection on the innate immune response to Zika. Keywords: Zika virus, monocytes, dengue virus, innate immunity, immune profiling, RNA-seq, CyTOF, network model, biomarker, Luminex
