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To gain functional insight into the host cellular genes required for virus infection, we performed whole\u2010blood RNA\u2010seq, 37\u2010plex mass cytometry of peripheral blood mononuclear cells (PBMCs), and serum cytokine measurements of acute\u2010 and convalescent\u2010phase samples obtained from 42 children naturally infected with CHIKV. Semi\u2010supervised classification and clustering of single\u2010cell events into 57 sub\u2010communities of canonical leukocyte phenotypes revealed a monocyte\u2010driven response to acute infection, with the greatest expansions in \u201cintermediate\u201d CD14\n                    <jats:sup>++<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    monocytes and an activated subpopulation of CD14\n                    <jats:sup>+<\/jats:sup>\n                    monocytes. Increases in acute\u2010phase CHIKV envelope protein E2 expression were highest for monocytes and dendritic cells. Serum cytokine measurements confirmed significant acute\u2010phase upregulation of monocyte chemoattractants. Distinct transcriptomic signatures were associated with infection timepoint, as well as convalescent\u2010phase anti\u2010CHIKV antibody titer, acute\u2010phase viremia, and symptom severity. We present a multiscale network that summarizes all observed modulations across cellular and transcriptomic levels and their interactions with clinical outcomes, providing a uniquely global view of the biomolecular landscape of human CHIKV infection.\n                  <\/jats:p>","DOI":"10.15252\/msb.20177862","type":"journal-article","created":{"date-parts":[[2018,8,27]],"date-time":"2018-08-27T10:25:31Z","timestamp":1535365531000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases"],"prefix":"10.1038","volume":"14","author":[{"given":"Daniela","family":"Michlmayr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1676-2523","authenticated-orcid":false,"given":"Theodore R","family":"Pak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeeb H","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u2010Ad David","family":"Amir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7436-7396","authenticated-orcid":false,"given":"Eun\u2010Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghee","family":"Kim\u2010Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Suprun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guajira P","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Balmaseda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0834-8178","authenticated-orcid":false,"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayte","family":"Suar\u00e9z\u2010Fari\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Wolinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kasarskis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-4037","authenticated-orcid":false,"given":"Eva","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,27]]},"reference":[{"key":"BFMSB177862_CR1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/sj.gene.6364173","volume":"6","author":"AR Abbas","year":"2005","unstructured":"Abbas AR, Baldwin D, Ma Y, Ouyang W, Gurney A, Martin F, Fong S, van Lookeren Campagne M, Godowski P, Williams PM, Chan AC, Clark HF (2005) Immune response in silico (IRIS): immune\u2010specific genes identified from a compendium of microarray expression data. 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