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Gastroenterology. 2018 Feb 2. pii: S0016-5085(18)30078-7. doi: 10.1053/j.gastro.2018.01.034. [Epub ahead of print]
Hepatitis B Virus Does Not Interfere with Innate Immune Responses in the Human Liver.Suslov A1, Boldanova T2, Wang X1, Wieland S3, Heim MH4.
Author information
1Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland.2Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Basel, Basel CH-4031, Switzerland.3Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland. Electronic address: [email protected].4Department of Biomedicine, University Hospital Basel, University of Basel, Basel CH-4031, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Basel, Basel CH-4031, Switzerland. Electronic address: [email protected].
AbstractBACKGROUND AND AIMS: Most viruses are detected at early stages of cell infection and induce an innate immune response mediated by production interferons (IFNs). IFNs induce expression of hundreds of IFN-stimulated genes (ISGs). Infection of chimpanzees with hepatitis C virus, but not hepatitis B virus (HBV), induces ISG expression in the liver. HBV might not induce an innate immune response because it is not detected by pattern recognition receptors (the stealth properties of HBV) or because HBV suppresses IFN production or signaling despite detection by pattern recognition receptors. We studied innate immune signaling in liver biopsies from patients with different stages of chronic HBV infection and uninfected individuals (controls).
METHODS: We obtained liver within 10 minutes after collection from 30 patients with chronic HBV infection (hepatitis B e antigen-positive or -negative, with or without hepatitis) and 42 controls (most with fatty liver disease). The liver tissues were analyzed by histology, immunohistochemistry, quantitative reverse-transcription PCR, in situ hybridization, HBV RNA quantification, and HBV genotyping; some specimens were incubated with toll-like receptor (TLR) ligands (poly [I:C]) or infected with Sendai virus and then analyzed.
RESULTS: Liver specimens from patients with HBV infection were not expressing more IFN or ISGs than those from control patients, indicating that chronic HBV infection did not activate an innate immune response. However, liver specimens from patients with HBV infection did produce IFN and induce expression of ISGs following activation of TLR3 with poly(I:C) or Sendai virus infections, so the innate immune response is not suppressed in these tissues.
CONCLUSION: Liver tissues from patients with chronic HBV infection do not have induction of an innate immune response, but this response can be activated by other factors (TLR3 binding, Sendai virus infection) in HBV-infected liver tissue. These findings support the hypothesis that HBV is invisible to pattern recognition receptors.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS: PAMP; PRR; ex vivo; virus immune evasion
PMID:29408639DOI:10.1053/j.gastro.2018.01.034
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