scholarly journals Tumor Necrosis Factor Alpha Inhibition of Hepatitis B Virus Replication Involves Disruption of Capsid Integrity through Activation of NF-κB

2003 ◽  
Vol 77 (7) ◽  
pp. 4033-4042 ◽  
Author(s):  
Michael Biermer ◽  
Robyn Puro ◽  
Robert J. Schneider
Keyword(s):  
Hepatitis B Virus ◽  
Tumor Necrosis Factor ◽  
Hepatitis B ◽  
Virus Replication ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
B Virus ◽  
Factor Alpha ◽  
Necrosis Factor

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.

scholarly journals Lack of Tumor Necrosis Factor Alpha Induces Impaired Proliferation of Hepatitis B Virus-Specific Cytotoxic T Lymphocytes

2003 ◽  
Vol 77 (4) ◽  
pp. 2469-2476 ◽  
Author(s):  
Senji Kasahara ◽  
Kazuki Ando ◽  
Kuniaki Saito ◽  
Kenji Sekikawa ◽  
Hiroyasu Ito ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Tumor Necrosis Factor ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
B Virus ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Recent studies have shown that tumor necrosis factor alpha (TNF-α) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-α knockout (TNF-α−/−) mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-α−/− mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-α−/− mice after two sessions of immunization with the HBV plasmid; however, TNF-α was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-α−/− mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-α enhanced the proliferation of a TNF-α−/− clone but suppressed that of a TNF-α+/+ clone in vitro, TNF-α also has a direct effect on the proliferation of CTLs. In conclusion, TNF-α is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.

scholarly journals DETEKSI GEN IL-6 DAN TNF-α DENGAN METODE PCR PADA PENDERITA HEPATITIS B DI LABORATORIUM KLINIK MAXIMA KOTA KENDARI

2021 ◽  
Vol 7 (1) ◽  
pp. 21-28
Author(s):  
Sanatang Abbas ◽  
Sri Anggarini Rasyid ◽  
Tiara Mayang Pratiwi Lio
Keyword(s):  
Tumor Necrosis Factor ◽  
Hepatitis B ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Virus Hepatitis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Polymerase Chain ◽  
Necrosis Factor

Penyakit Hepatitis B adalah inflamasi yang terjadi pada organ hati yang dapat disebabkan oleh virus hepatitis B. Pada saat terjadi inflamasi sitokin yang ada dalam tubuh akan merespon atau mengenali jenis patogen berupa virus yang masuk ke dalam tubuh. Tumor Necrosis Factor (TNF-α) adalah salah satu sitokin pro-inflamasi yang berperan dalam proses inflamasi hati, dan Interleukin-6 (IL-6) adalah sitokin yang disekresikan dari jaringan tubuh pada fase infeksi akut atau kronik. Tujuan dari penelitian ini adalah untuk mendeteksi gen TNF-α dan IL-6 pada penderita hepatitis B dengan metode polymerase chain reaction (PCR). Jenis penelitian yang digunakan dalam penelitian ini adalah semi kuantitatif, dengan desain penelitian eksperimental. Populasi pada penelitian adalah seluruh penderita suspek yang melakukan pemeriksaan rapid Hepatitis B (HbsAg) di Laboratorium Klinik Maxima Kota Kendari sebanyak 7 orang. Teknik penarikan sampel menggunakan total sampling dengan kriteria inklusi sampel yaitu pasien yang tidak memiliki riwayat penyakit lain selain hepatitis B. Berdasarkan hasil penelitian diketahui bahwa dari ketujuh sampel penderita hepatitis B yang diperiksa menggunakan metode PCR 3 sampel dengan hasil positif (45%) terhadap gen TNF-α dan 7 (100%) hasil negative terhadap gen Interleukin 6 (IL-6). Sehingga dapat di simpulkan bahwa jenis sitokin yang berperan saat terjadi inflamasi ketika seseorang terinfeksi Virus Hepatitis B adalah Tumor Necrosis Factor Alpha (TNF-α).

Possible Reactivation of Potential Hepatitis B Virus Occult Infection by Tumor Necrosis Factor-α Blocker in the Treatment of Rheumatic Diseases

2009 ◽  
Vol 37 (2) ◽  
pp. 346-350 ◽  
Author(s):  
YUN JUNG KIM ◽  
SANG-CHEOL BAE ◽  
YOON-KYOUNG SUNG ◽  
TAE-HWAN KIM ◽  
JAE-BUM JUN ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Tumor Necrosis Factor ◽  
Hepatitis B ◽  
Rheumatic Diseases ◽  
Tumor Necrosis ◽  
Hbv Infection ◽  
Occult Infection ◽  
Tnf Α ◽  
B Virus ◽  
Necrosis Factor

Objective. To assess the safety of anti-tumor necrosis factor (TNF-α) therapy in patients with rheumatic diseases in terms of the reactivation of potential hepatitis B virus (HBV) occult infection.Methods. Patients who had taken anti-TNF-α for the treatment of rheumatic diseases from January 2002 to May 2008 were included in the study. In this patient group, we retrospectively investigated a series of serum aminotransferase levels, HBV serologic status, the type of anti-TNF-α therapy, duration of the anti-TNF-α treatment, and concurrent use of hepatotoxic drugs.Results. A total of 266 cases were documented using 3 serologic markers for HBV infection: HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), and HBV core IgG Ab (HBcAb). Of these, 8 cases had chronic hepatitis B (HBsAg+), 170 cases were HBcAb-negative, and 88 cases were identified as having potential HBV occult infections represented by HBsAg-negative and HBcAb-positive, irrespective of the status of the HBsAb.The frequency of clinically significant (> 2 times normal value) and persistent increase (> 2 consecutive tests) of aminotransferase levels was significantly higher in the group with a potential HBV occult infection compared to the HBcAb-negative group. In the multiple logistic regression analysis controlling for various potential confounding factors such as prophylactic anti-tuberculosis medication, methotrexate, nonsteroidal antiinflammatory drugs, and the type of anti-TNF-α therapy, only potential HBV occult infection was a significant risk factor for abnormal liver function test (LFT).Conclusion. All rheumatic patients who plan to take anti-TNF-α treatment should undergo a test for HBV serology, including HBcAb, and have a close followup with an LFT test during therapy. Further prospective studies for hepatitis B viral load using HBV-polymerase chain reaction in patients who are HbcAb positive are needed to identify whether the abnormal LFT comes from the reactivation of occult HBV infection.

scholarly journals Rhinovirus Replication in Human Macrophages Induces NF-κB-Dependent Tumor Necrosis Factor Alpha Production

2006 ◽  
Vol 80 (16) ◽  
pp. 8248-8258 ◽  
Author(s):  
Vasile Laza-Stanca ◽  
Luminita A. Stanciu ◽  
Simon D. Message ◽  
Michael R. Edwards ◽  
James E. Gern ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Virus Replication ◽  
Tumor Necrosis ◽  
Nuclear Translocation ◽  
Necrosis Factor Alpha ◽  
Human Macrophages ◽  
Tnf Α ◽  
Acute Exacerbations ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Rhinoviruses (RV) are the major cause of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Rhinoviruses have been shown to activate macrophages, but rhinovirus replication in macrophages has not been reported. Tumor necrosis factor alpha (TNF-α) is implicated in the pathogenesis of acute exacerbations, but its cellular source and mechanisms of induction by virus infection are unclear. We hypothesized that rhinovirus replication in human macrophages causes activation and nuclear translocation of NF-κB, leading to TNF-α production. Using macrophages derived from the human monocytic cell line THP-1 and from primary human monocytes, we demonstrated that rhinovirus replication was productive in THP-1 macrophages, leading to release of infectious virus into supernatants, but was limited in monocyte-derived macrophages, likely due to type I interferon production, which was robust in monocyte-derived but deficient in THP-1-derived macrophages. Similar to bronchial epithelial cells, only small numbers of cells supported complete virus replication. We demonstrated RV-induced activation of NF-κB and colocalization of p65/NF-κB nuclear translocation with virus replication in both macrophage types. The infection induced TNF-α release in a time- and dose-dependent, RV serotype- and receptor-independent manner and was largely (THP-1 derived) or completely (monocyte derived) dependent upon virus replication. Finally, we established the requirement for NF-κB but not p38 mitogen-activated protein kinase in induction of TNF-α. These data suggest RV infection of macrophages may be an important source of proinflammatory cytokines implicated in the pathogenesis of exacerbations of asthma and COPD. They also confirm inhibition of NF-κB as a promising target for development of new therapeutic intervention strategies.

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