Suppression of hepatitis B virus replication in Tupaia hepatocytes by tumor necrosis factor alpha of Tupaia belangeri

ABSTRACT Chronic infection by hepatitis B virus results from an inability to clear the virus, which is associated with liver disease and liver cancer. Tumor necrosis factor alpha (TNF-α) is associated with noncytopathic clearance of hepatitis B virus in animal models. Here we demonstrate that the nuclear factor κB (NF-κB) signaling pathway is a central mediator of inhibition of hepatitis B virus by TNF-α and we describe the molecular mechanism. TNF-α is shown to suppress hepatitis B virus DNA replication without cell killing by disrupting the formation or stability of cytoplasmic viral capsids through a pathway requiring the NF-κB-activating inhibitor of κB kinase complex IKK-α/β and active transcription factor NF-κB. Hepatitis B virus replication could also be inhibited and viral capsid formation could be disrupted in the absence of TNF-α solely by overexpression of IKK-α/β or strong activation of NF-κB. In contrast, inhibition of NF-κB signaling stimulated viral replication, demonstrating that HBV replication is both positively and negatively regulated by the level of activity of the NF-κB pathway. Studies are presented that exclude the possibility that HBV inhibition by NF-κB is carried out by secondary production of gamma interferon or alpha/beta interferon. These results identify a novel mechanism for noncytopathic suppression of hepatitis B virus replication that is mediated by the NF-κB signaling pathway and activated by TNF-α.

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Tumor necrosis factor-$alpha; and interferon-$gamma; synergistically inhibit hepatitis B virus replication in HB611 cells

Hepatology ◽

10.1016/0270-9139(93)91998-8 ◽

1993 ◽

Vol 18 (4) ◽

pp. A117

Author(s):

Y KAWANISHI

Keyword(s):

Hepatitis B Virus ◽

Tumor Necrosis Factor ◽

Hepatitis B ◽

Interferon Gamma ◽

Virus Replication ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

B Virus ◽

Factor Alpha ◽

Necrosis Factor

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Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice.

Journal of Virology ◽

10.1128/jvi.66.6.3955-3960.1992 ◽

1992 ◽

Vol 66 (6) ◽

pp. 3955-3960 ◽

Cited By ~ 93

Author(s):

P N Gilles ◽

G Fey ◽

F V Chisari

Keyword(s):

Gene Expression ◽

Hepatitis B Virus ◽

Tumor Necrosis Factor ◽

Hepatitis B ◽

Transgenic Mice ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

B Virus ◽

Factor Alpha ◽

Necrosis Factor

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P548 Hepatitis B virus reactivation in hepatitis B virus infected patients with inflammatory bowel disease receiving anti-tumor necrosis factor-alpha therapy

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.672 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S359-S359

Author(s):

J.M. Lee ◽

K.-M. Lee ◽

H.-S. Kim ◽

B.D. Ye ◽

S.J. Park ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Tumor Necrosis ◽

Virus Reactivation ◽

Necrosis Factor Alpha ◽

B Virus ◽

Inflammatory Bowel ◽

Factor Alpha ◽

Alpha Therapy ◽

Necrosis Factor

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Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

Case Reports in Gastroenterology ◽

10.1159/000358554 ◽

2014 ◽

Vol 8 (1) ◽

pp. 44-50 ◽

Cited By ~ 1

Author(s):

Tetsuya Ishida ◽

Hideyasu Nagamatsu ◽

Tetsuya Ueo ◽

Ryoichi Narita ◽

Ken Takahashi ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Hepatitis B ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

De Novo ◽

Necrosis Factor Alpha ◽

De Novo Hepatitis B ◽

Factor Alpha ◽

Alpha Therapy ◽

Necrosis Factor

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INFLUENCE OF AUTOLEUKOCYTE VACCINATION ON ACTIVITY LEVEL OF TUMOR NECROSIS FACTOR ALPHA IN PATIENTS WITH CHRONIC HEPATITIS B

Wiadomości Lekarskie ◽

10.36740/wlek201901106 ◽

2019 ◽

Vol 72 (1) ◽

pp. 31-34

Author(s):

Alexandr Zinchuk ◽

Oleksandr Herasun ◽

Andrij Zadorozhnyi ◽

Olga Vorozhbyt ◽

Borys Gerasun

Keyword(s):

Chronic Hepatitis ◽

Tumor Necrosis Factor ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Inflammatory Cytokine ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

Introduction: data about influence of intradermal vaccination with native autoleukocytes on activity level of pro-inflammatory cytokine tumor necrosis factor alpha in patients with chronic hepatitis B have been presented in the article. The aim: Based on positive results, obtained from autoleukocyte immunization in patients with psoriasis [14], the aim of our research was to use and study such therapy for reducing the synthesis of pro-inflammatory cytokine TNF-α in patients with chronic hepatitis B (chronic hepatitis B). Materials and methods: Patients with chronic hepatitis B with high level of tumor necrosis factor alpha (≥30pg/ml) were vaccinated with native autoleukocytes (23); simultaneously, the same procedure was performed to patients (11) with low level of this cytokine (5pg/ml). Leukocytes were isolated from heparinized peripheral venous blood of a patient with hepatitis B by centrifuging plasma, obtained after blood precipitation for 140-160 minutes at temperature 370 С. The suspension was resuspended in 1-1.5 ml of a patient’s blood serum and injected into the skin of the back in the dose 0.1 ml. Results: in 30 days after immunization, reduction of tumor necrosis factor alpha was observed in all patients with its high level (100%), in 65.25% of individuals – to 5 pg/ml; in some patients, who had low or average level of pro-inflammatory cytokine, the level individually increased (41.67%). Conclusions: The elaborated method of influence on activity of tumor necrosis factor alpha in patients with chronic hepatitis B is effective and worth implementing into clinical practice.

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Association of tumor necrosis factor alpha -238G/A and -308G/A promotor polymorphisms with clearance of Hepatitis B virus infection in Turkish population

Acta Medica ◽

10.32552/2019.actamedica.341 ◽

2019 ◽

Vol 50 (1) ◽

pp. 1-6

Author(s):

Ahmet Çağkan İnkaya ◽

Emel Türk Arıbaş ◽

İbrahim Erayman ◽

Hasan Acar ◽

Bahar Kandemir ◽

...

Keyword(s):

Chronic Hepatitis ◽

Tumor Necrosis Factor ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Natural Immunity ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

Aim: Acute viral hepatitis B may lead to chronic hepatitis in 6% of adult population. We compared the frequency of Tumor necrosis factor alpha promotor polymorphisms in chronic hepatitis B patients and people with natural immunity against hepatitis B. Material and Methodology: Chronic hepatitis B patients and age matched control cases with natural immunity to hepatitis B virus were recruited 1:1 in this study. Tumor necrosis factor alpha -238G/A and -308G/A polymorphisms were studied with PCR-RFLP. χ2 test was performed in statistical analysis. Results: A total of 101 volunteers enrolled in two study groups. Thirty-eight men and 12 women constituted the chronic hepatitis B patient group and 40 men and 11 women recruited in natural immunity group. Frequency of -238G allele was 87.5% and 97% in chronic hepatitis B and natural immunity groups, respectively. Frequency of -308G allel was 93% and 92.1% in chronic hepatitis B and natural immunity groups, respectively. Frequencies of polymorphisms at positions -238 and -308 in the promotor of tumor necrosis factor alpha gene were not different between chronic hepatitis B and natural immunity groups. Conclusion: Tumor necrosis factor alpha promoter polymorphisms at -238 and -308 positions do not effect the outcome hepatitis B infection in Turkish population. Clearance of hepatitis B virus infection is multifactorial. Thus, further studies needed to identify genetic predisposition to chronic hepatitis B infection.

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