A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela.
Aaron F CarlinJinsheng WenEdward A VizcarraMelanie McCauleyAntoine ChaillonKevan AkramiCheryl KimAnnie Elong NgonoMaria Luz Lara-MarquezDavey M SmithChristopher K GlassRobert T SchooleyChristopher BennerSujan ShrestaPublished in: PLoS neglected tropical diseases (2018)
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus linked to devastating neurologic diseases. Immune responses to flaviviruses may be pathogenic or protective. Our understanding of human immune responses to ZIKV in vivo remains limited. Therefore, we performed a longitudinal molecular and phenotypic characterization of innate and adaptive immune responses during an acute ZIKV infection. We found that innate immune transcriptional and genomic responses were both cell type- and time-dependent. While interferon stimulated gene induction was common to all innate immune cells, the upregulation of important inflammatory cytokine genes was primarily limited to monocyte subsets. Additionally, genomic analysis revealed substantial chromatin remodeling at sites containing cell-type specific transcription factor binding motifs that may explain the observed changes in gene expression. In this dengue virus-experienced individual, adaptive immune responses were rapidly mobilized with T cell transcriptional activity and ZIKV neutralizing antibody responses peaking 6 days after the onset of symptoms. Collectively this study characterizes the development and resolution of an in vivo human immune response to acute ZIKV infection in an individual with pre-existing flavivirus immunity.
Keyphrases
- zika virus
- immune response
- dengue virus
- gene expression
- transcription factor
- dendritic cells
- aedes aegypti
- liver failure
- endothelial cells
- respiratory failure
- genome wide
- peripheral blood
- toll like receptor
- genome wide identification
- dna methylation
- induced pluripotent stem cells
- dna binding
- copy number
- oxidative stress
- intensive care unit
- cell proliferation
- dna damage
- mechanical ventilation
- depressive symptoms
- signaling pathway
- acute respiratory distress syndrome
- heat shock
- physical activity