Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance

Abstract

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.

Calves Infected with Virulent and Attenuated Mycoplasma bovis Strains Have Upregulated Th17 Inflammatory and Th1 Protective Responses, Respectively

“…Thus, these two strains can serve as ideal materials to investigate the factors of M. bovis pathogenesis. Furthermore, PBMCs are clinically relevant cells with well-established roles in host immune responses to microbial pathogens [16]. The objective of this study was to reveal the underlying mechanism for pathogenesis of virulent P1 strain and immunity of attenuated P150 strain by performing a comparative transcriptome analysis of PBMCs from calves infected with both strains and confirming the transcriptome findings using the data from the blood and lung tissues and gross pathology of the experimental cattle.…”

MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

“…Also, the dysfunction of HCV-infected PBMCs leads to immune function decline, and it becomes more difficult for the host to clear intrahepatic HCV [16]. Moreover, recent studies have shown that PBMCs may reflect the alterations of intracellular pathways occurring during HCV-related liver diseases [17], being the innate antiviral response against acute HCV not restricted to the liver [18].…”

Hepatitis C Virus as a Unique Human Model Disease to Define Differences in the Transcriptional Landscape of T Cells in Acute versus Chronic Infection

“…We will also learn about vertical regulation of T cell processes through epigenetic, transcriptional, translational, and post-translational processes. These insights will help understand cross-talk between T cells and different immune cell types or other components of the host immune response by integrating data from many different emerging studies [90] as well as using unbiased parallel analysis of different immune cells with technologies such as 10x or Seq-Well. There has never been a more exciting time to study HCV immunology.…”