TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism

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Hepatitis C virus (HCV) patients have increased levels of circulating tumor necrosis factor-α (TNF-α). In this report, we demonstrate that HCV can directly induce the expression of TNF-α in hepatocytes in a biphasic manner via NF-κB. The induction of TNF-α by HCV in the first phase is prompt, requires no HCV gene expression and is dependent on TLR7 and TLR8 and their downstream effectors. TNF-α induced by HCV supports interferon signaling via an autocrine mechanism and suppresses HCV replication, as abolishing the expression of TNF-α or its receptor TNFR1 results in the loss of IFNAR2, a subunit of the type I interferon receptor, and an increase of HCV replication. Our studies thus reveal an interesting interplay between HCV and hepatocytes, with the virus attempting to blunt the IFN response by depleting IFNAR2 and the host cell overcoming this blunting effect of HCV by using TNF-α to restore the expression of IFNAR2.

Vyšlo v časopise: TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004937
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004937

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