Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

I. Tsu Chyuan, Huei-Fang Tsai, Horng Tay Tzeng, Chi Chang Sung, Chien Sheng Wu, Pei Jer Chen, Ping Ning Hsu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hepatitis B virus (HBV) reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor (TNF) blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-α blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-α blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-α blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose- and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-α blockage therapy occurred at early time points after HBV infection. In addition, TNF-α blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death (PD)-1 high CD127 low exhausted T cells. Furthermore, TNF-α blockade abolished Toll-like receptor 9 (TLR9) ligand-induced facilitation of HBV viral clearance. Taken together, TNF-α blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-α blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during therapy with TNF-α-blocking agents.

Original languageEnglish
Pages (from-to)317-325
Number of pages9
JournalCellular and Molecular Immunology
Volume12
Issue number3
DOIs
Publication statusPublished - May 7 2015

Fingerprint

Hepatitis B
Hepatitis B virus
Tumor Necrosis Factor-alpha
T-Lymphocytes
Therapeutics
Viral Load
Virus Diseases
Toll-Like Receptor 9
Recurrence
Adaptive Immunity
Innate Immunity
Immunosuppression
Autoimmune Diseases

Keywords

  • HBV viral load
  • hepatitis B virus
  • tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model. / Chyuan, I. Tsu; Tsai, Huei-Fang; Tzeng, Horng Tay; Sung, Chi Chang; Wu, Chien Sheng; Chen, Pei Jer; Hsu, Ping Ning.

In: Cellular and Molecular Immunology, Vol. 12, No. 3, 07.05.2015, p. 317-325.

Research output: Contribution to journalArticle

Chyuan, I. Tsu ; Tsai, Huei-Fang ; Tzeng, Horng Tay ; Sung, Chi Chang ; Wu, Chien Sheng ; Chen, Pei Jer ; Hsu, Ping Ning. / Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model. In: Cellular and Molecular Immunology. 2015 ; Vol. 12, No. 3. pp. 317-325.
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