Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection

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 to characterize immune function in peripheral blood 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. This innate response coincides with a decrease in B cell transcriptional signatures. These results represent the first longitudinal transcriptomic characterization of human immune function in acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure. mRNA-Seq of peripheral blood mononuclear cells (PBMC) collected from individuals before, during, and after acute HCV infection. Acute HCV infection resulted in spotaneous viral resolution (n=6) or chronic infection (n=8). Four time points were examined per subject: i) Pre-infection baseline (Variable); ii) Early acute (2-9 weeks, mean 6 weeks); iii) Late acute (15 – 20 weeks, mean 17 weeks); and iv) Follow up (25 – 71 weeks, mean 52 weeks)