Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

Abstract

BackgroundInfection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance.MethodsPlasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV.ResultsWe have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions.ConclusionsThese results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

“…Considering coinfection as a simultaneous phenomenon or as a repeated occurrence due to the continued use of parenteral drugs in some of these individuals, the larger HIV reservoir initially observed was likely due to a potent anti-HCV immune response in the spontaneous clarifiers. This immune activation is able to eliminate HCV infection but may also favor the persistence of the HIV reservoir, since parameters such as CD4+ T cell activation, NF-κβ signaling and IFN-γ are significantly elevated [35][36][37]. This immune response is normalized once HCV has cleared [35].…”