Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation

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Globally, approximately 200 million people are persistently infected with Hepatitis C virus (HCV). Mechanisms by which HCV establishes persistent infection are complex, and several host and viral factors appear to contribute to the ability of HCV to evade immune clearance. T cell activation through the T cell receptor (TCR) is an essential first step in the generation of an adaptive immune response. Although HCV infection is associated with impaired T cell function, the mechanisms for this dysfunction are poorly understood. Here, we demonstrate that HCV particles inhibit T cell activation by interfering with proximal and distal signals that are triggered by activation through the TCR. First, HCV envelope (E2) RNA was processed into a small RNA that targeted a regulatory phosphatase, inhibiting proximal TCR signaling. Second, the lymphocyte specific Src kinase (Lck) phosphorylated HCV E2 at tyrosine 613 (Y613), and phospho-E2 inhibited nuclear translocation of activated NFAT, reducing distal TCR activation signals. The RNA and protein motifs involved are highly conserved among all HCV isolates, and mutation restored TCR signaling. Thus, HCV particles interfere with TCR signaling and impair T cell activation using two distinct mechanisms. This may contribute to HCV persistence and T cell dysfunction during HCV infection.

Vyšlo v časopise: Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005183
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005183

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