Natural History of Chronic Hepatitis B

McMahon, Brian J.

doi:10.1016/j.cld.2010.05.007

Cited by 168 publications

(137 citation statements)

References 74 publications

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“…2 Hepatitis B virus (HBV) is a noncytopathic, hepatotropic DNA virus and a major pathogen causing liver disease worldwide. 4 Although HBV vaccines have reduced the number of new HBV infections, they do not benefit patients with chronic HBV infection, who have a high risk for the development of liver cirrhosis and hepatocellular carcinoma. 5 HBV X protein (HBx) is an essential viral protein that is required for successful replication and maintenance of viral infection in mouse models and various cultured cell systems.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus–triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response

et al. 2016

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Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagymediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virusinfected cells. We demonstrate that the expression of the TNFRSF10B protein is dramatically reduced both in liver tissues of chronic hepatitis B patients and in cell lines transfected with HBV or HBx. HBx-mediated downregulation of TNFRSF10B is caused by the lysosomal, but not proteasomal, degradation pathway. Immunoblotting analysis of LC3B and SQSTM1, and microscopy analysis of tandem-fluorescence-tagged LC3B revealed that HBx promotes complete autophagy. Inhibition of autophagy with a pharmacological inhibitor and LC3B knockdown revealed that HBx-induced autophagy is crucial for TNFRSF10B degradation. Immunoprecipitation and GST affinity isolation assays showed that HBx directly interacts with TNFRSF10B and recruits it to phagophores, the precursors to autophagosomes. We confirmed that autophagy activation is related to the downregulation of the TNFRSF10B protein in liver tissues of chronic hepatitis B patients. Inhibition of autophagy enhanced the susceptibility of HBx-infected hepatocytes to TNFSF10. These results identify the dual function of HBx in TNFRSF10B degradation: HBx plays a role as an autophagy receptor-like molecule, which promotes the association of TNFRSF10B with LC3B; HBx is also an autophagy inducer. Our data suggest a molecular mechanism for HBV evasion from TNFSF10-mediated antiviral immunity, which may contribute to chronic HBV infection.

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Section: Introductionmentioning

confidence: 99%

Hepatitis B virus–triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response

et al. 2016

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“…Patients with lower serum level of HBsAg are more prone to spontaneous clearance of HBsAg. This reflects an immunological control of the infection with both humoral antibody responses to hepatitis B virus (HBV) envelope antigens for neutralizing the virus as well as cellmediated immunity eliminating HBV-infected cells in a noncytopathic pathway (3,6,7). Type I interferons (IFNIs), known as IFN-a/b, make the first line of innate immunity in response to host defense against viruses and exclusive intracellular pathogens (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, HBsAg clearance is an extremely favorable event in the course of CHB. Therefore, great attention has been paid to find determinants of spontaneous HBsAg clearance (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Higher Serum Levels of Type I Interferon Receptor in Adults with Chronic Hepatitis B Leading to Hepatitis B Surface Antigen Clearance

Ashraf

Besharat

Rad

et al. 2017

Jundishapur J Microbiol

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“…The first phase of HBV is immune tolerance McMahon, 2008;Merican et al, 2000;Wright, 2006). During this phase, patients are hepatitis B e-antigen (HBeAg) positive and have high levels of serum HBV DNA (ranges between 10 7 -10 11 copies/mL) McMahon, 2008;Merican et al, 2000;Wright, 2006).…”

mentioning

confidence: 99%

“…The natural history of HBV infection has three phases including immune tolerance, immune clearance and a residual phase McMahon, 2008;Wright, 2006). The first phase of HBV is immune tolerance McMahon, 2008;Merican et al, 2000;Wright, 2006).…”

mentioning

confidence: 99%

Reviews on the Epidemiology, Quality of Life, and Management of Chronic Hepatitis B (CHB)

Lam¹,

Lam²

2012

Hepatocellular Carcinoma - Basic Research

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Natural History of Chronic Hepatitis B

Cited by 168 publications

References 74 publications

Hepatitis B virus–triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response

Hepatitis B virus–triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response

Higher Serum Levels of Type I Interferon Receptor in Adults with Chronic Hepatitis B Leading to Hepatitis B Surface Antigen Clearance

Reviews on the Epidemiology, Quality of Life, and Management of Chronic Hepatitis B (CHB)

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