Open AccessComprehensive innate immune profiling of chikungunya virus infection in pediatric cases
Author(s) -
Michlmayr Daniela,
Pak Theodore R,
Rahman Adeeb H,
Amir ElAd David,
Kim EunYoung,
KimSchulze Seunghee,
Suprun Maria,
Stewart Michael G,
Thomas Guajira P,
Balmaseda Angel,
Wang Li,
Zhu Jun,
SuarézFariñas Mayte,
Wolinsky Steven M,
Kasarskis Andrew,
Harris Eva
Publication year - 2018
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20177862
Subject(s) - biology , cd14 , immunology , virology , virus , innate immune system , chikungunya , immune system , monocyte , peripheral blood mononuclear cell , cd16 , viremia , chemokine , cd8 , biochemistry , cd3 , in vitro
Chikungunya virus ( CHIKV ) is a mosquito‐borne alphavirus that causes global epidemics of debilitating disease worldwide. To gain functional insight into the host cellular genes required for virus infection, we performed whole‐blood RNA ‐seq, 37‐plex mass cytometry of peripheral blood mononuclear cells ( PBMC s), and serum cytokine measurements of acute‐ and convalescent‐phase samples obtained from 42 children naturally infected with CHIKV . Semi‐supervised classification and clustering of single‐cell events into 57 sub‐communities of canonical leukocyte phenotypes revealed a monocyte‐driven response to acute infection, with the greatest expansions in “intermediate” CD 14 ++ CD 16 + monocytes and an activated subpopulation of CD 14 + monocytes. Increases in acute‐phase CHIKV envelope protein E2 expression were highest for monocytes and dendritic cells. Serum cytokine measurements confirmed significant acute‐phase upregulation of monocyte chemoattractants. Distinct transcriptomic signatures were associated with infection timepoint, as well as convalescent‐phase anti‐ CHIKV antibody titer, acute‐phase 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.