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Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model.

PloS one (2014-07-23)
Horng-Tay Tzeng, Hwei-Fang Tsai, I-Tsu Chyuan, Hsiu-Jung Liao, Chun-Jen Chen, Pei-Jer Chen, Ping-Ning Hsu
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rat Tumor Necrosis Factor α ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Rat Tumor Necrosis Factor α ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Bovine TNFα / Tumor Necrosis Factor alpha ELISA Kit, for serum, plasma and cell culture supernatants
Sigma-Aldrich
Human Tumor Necrosis Factor α ELISA Kit, for serum, plasma, cell culture supernatants and urine
Sigma-Aldrich
Mouse Tumor Necrosis Factor α ELISA Kit, for serum, plasma and cell culture supernatant