Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model
Journal
PLoS ONE
Journal Volume
9
Journal Issue
7
Date Issued
2014
Author(s)
Abstract
Persistent hepatitis B viral (HBV) infection results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). An efficient control of virus infections requires the coordinated actions of both innate and adaptive immune responses. In order to define the role of innate immunity effectors against HBV, viral clearance was studied in a panel of immunodeficient mouse strains by the hydrodynamic injection approach. Our results demonstrate that HBV viral clearance is not changed in IFN-α/β receptor (IFNAR), RIG-I, MDA5, MYD88, NLRP3, ASC, and IL-1R knock-out mice, indicating that these innate immunity effectors are not required for HBV clearance. In contrast, HBV persists in the absence of tumor necrosis factor-alpha (TNF-α) or in mice treated with the soluble TNF receptor blocker, Etanercept. In these mice, there was an increase in PD-1-expressing CD8+ T-cells and an increase of serum HBV DNA, HBV core, and surface antigen expression as well as viral replication within the liver. Furthermore, the induction of TNF-α in clearing HBV is dependent on the HBV core, and TNF blockage eliminated HBV core-induced viral clearance effects. Finally, the intra-hepatic leukocytes (IHLs), but not the hepatocytes, are the cell source responsible for TNF-α production induced by HBcAg. These results provide evidences for TNF-α mediated innate immune mechanisms in HBV clearance and explain the mechanism of HBV reactivation during therapy with TNF blockage agents. ? 2014 Tzeng et al.
SDGs
Other Subjects
alpha interferon receptor; ASC protein; beta interferon receptor; cryopyrin; etanercept; hepatitis B core antigen; hepatitis B surface antigen; interleukin 1 receptor; MDA5 protein; myeloid differentiation factor 88; programmed death 1 receptor; retinoic acid inducible protein I; tumor necrosis factor alpha; unclassified drug; virus DNA; hepatitis B core antigen; tumor necrosis factor alpha; animal experiment; animal model; animal tissue; article; CD8+ T lymphocyte; controlled study; gene expression; Hepatitis B virus; immune response; innate immunity; intra hepatic leukocyte; knockout mouse; leukocyte; male; mouse; nonhuman; persistent virus infection; protein expression; protein synthesis; viral clearance; virus core; virus gene; virus load; virus reactivation; virus replication; animal; disease model; Hepatitis B virus; immunology; innate immunity; liver; metabolism; Animals; Disease Models, Animal; Hepatitis B Core Antigens; Hepatitis B virus; Immunity, Innate; Liver; Mice; Tumor Necrosis Factor-alpha; Virus Replication
Publisher
Public Library of Science
Type
journal article