[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela
Aaron F. Carlin , Jinsheng Wen , Edward A. Vizcarra , Melanie McCauley, Antoine Chaillon, Kevan Akrami, Cheryl Kim, Annie Elong Ngono, Maria Luz Lara-Marquez, Davey M. Smith, Christopher K. Glass, Robert T. Schooley, Christopher Benner, Sujan Shresta
Published: December 31, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0007053 / This is an uncorrected proof.
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.
Zika virus (ZIKV) is an emerging flaviviral infection that causes significant clinical disease. It is estimated that approximately one half of the world’s population is at risk for ZIKV infection. There are only a limited number of studies describing the human immune response to ZIKV infection. Carlin et al. combined conventional and genomic approaches to longitudinally analyze the innate and adaptive immune responses to acute ZIKV infection and its resolution in a person who was infected while traveling in Venezuela during the 2016 ZIKV epidemic year. Genome-wide sequencing in individual cell types revealed that although many populations respond to interferon stimulation, only specific cell populations within peripheral blood mononuclear cells upregulate important inflammatory cytokine gene expression. Additionally, analysis of open chromatin using ATAC-seq suggests that chromatin remodeling at sites containing cell-type specific transcription factor binding motifs may help us understand changes in gene expression. Consistent with previous reports, this individual with prior exposure to dengue virus (DENV), rapidly developed neutralizing anti-ZIKV responses that were cross-reactive with multiple DENV serotypes. Collectively this study combines traditional and genomic approaches to characterize the cell-type specific development of an in vivo human immune response to acute ZIKV infection.
Citation: Carlin AF, Wen J, Vizcarra EA, McCauley M, Chaillon A, Akrami K, et al. (2018) A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela. PLoS Negl Trop Dis 12(12): e0007053. https://doi.org/10.1371/journal.pntd.0007053
Editor: William B. Messer, Oregon Health and Science University, UNITED STATES
Received: May 11, 2018; Accepted: December 5, 2018; Published: December 31, 2018
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Data Availability: All human RNA-seq and ATAC-seq data described in this manuscript are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus(GEO) accession number GSE123541.
Funding: This research was supported by NIAID/NIH grants AI116813 and AI140063 and the La Jolla Institute for Immunology institutional support to SS, KL2 Scholars: 1KL2TR001444 and Burroughs Wellcome Career Award for Medical Scientists to AFC, and NIAID/NIH AI036214 to DMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors declare that there are no competing interest.
Keywords: Flavivirus; Zika Virus; Immunology.