Open AccessLongitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance
Author(s) -
Brad R. Rosenberg,
Marion Depla,
Catherine A. Freije,
Denis Gaucher,
Sabrina Mazouz,
Maude Boisvert,
Nathalie Bédard,
Julie Bruneau,
Charles M. Rice,
Naglaa H. Shoukry
Publication year - 2018
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1007290
Subject(s) - innate immune system , immune system , immunology , hepatitis c virus , virology , biology , virus , transcriptome , dengue virus , interferon , dengue fever , peripheral blood mononuclear cell , gene expression , gene , biochemistry , in vitro
Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure.