HCV Infection Enhances Th17 Commitment, Which Could Affect the Pathogenesis of Autoimmune Diseases

Abstract

BackgroundVarious kinds of autoimmune diseases have been reported to have a significant relationship with persistent hepatitis c virus (HCV) infection and Th17 cells. Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation.MethodsTherefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro.ResultsThe prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C) was significantly higher than in other types of chronic hepatitis (hepatitis B and NASH). A significantly higher frequency of IL6 and TGF-β double-high patients was detected in CH-C than in other liver diseases. Moreover, these double-high patients had significantly higher positivity of anti-nuclear antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-β, IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1b lymphotropic HCV (Ly-HCV), by deep sequencing analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells with various kinds of cytokine-conditions including IL1β, IL23, IL6 and TGF-β in vitro. Infection by HCV could significantly enhance the development of Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core protein, which could enhance the STAT-3 signaling and up-regulate the expression of RORγt as a Th17 master gene.ConclusionInfection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.

Interleukin-17A and B-cell activating factor in chronic hepatitis C patients with or without asymptomatic mixed cryoglobulinemia: effects of antiviral treatment and correlations with vitamin D

“…We observed a significant increase in the IL-17A levels in HCV-infected patients compared to HC, confirming recent reports [ 27 , 28 ]. Interestingly, further analysis showed high levels of IL-17A in patients who responded to antiviral treatment versus non-responders [ 29 ].…”

Baseline quasispecies selection and novel mutations contribute to emerging resistance-associated substitutions in hepatitis C virus after direct-acting antiviral treatment

“…Human serum albumin levels were measured using ELISA with the Human Albumin ELISA Quantitation Set (Bethyl Laboratories Inc., TX). The mice were infected with HCV using the following two methods: (1) intravenous injection via tail vein with 100 μl of hepatitis C from a patient serum (DAA-naïve, genotype 1b, 6.8 log IU/ml) or (2) intrahepatic injection with 100 μg of engineered full-genome HCV RNA (Ly-HCV 26 , wild type from genotype 1b HCV, accession No. AB779562) in 400 μl of PBS.…”

Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2

“…HCV promoted the adhesion of primary B cells to Huh-7 cells for retention of B cells on infected hepatocytes, thus implying that B cells may provide a vehicle for HCV persistence by transmission to the liver. Additionally, lymphotropism of HCV (SB strain: patient splenoma B-cell-derived isolated by our group) is not limited to B cells since we have identified HCV infection (SB strain) of T cells and subsequent alterations in their functions89. These studies, however, did not provide conclusive evidence that other molecules on other immune cell types serve as HCV co-receptors.…”