The Interactions Between HBV and the Innate Immunity of Hepatocytes

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

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“…MAVS then links RIG-I to IKKi and TBK1 activation. The role of MAVS/IPS-1 is essential for induction of IFN by cytosolic DNA [ 132 , 133 ].…”

Section: Viral Infections and Mitochondrial Biogenesismentioning

confidence: 99%

Role of Mitochondria in Viral Infections

Elesela

Lukacs

2021

Life

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“…Hepatitis B virus (HBV), a member of the Hepadnaviridae family, is one of the smallest enveloped animal DNA viruses and the pathogen to cause Hepatitis B. Although HBV vaccines and effective antiviral drugs have been available for more than 20 years, chronic HBV infection (CHB) remains a global public health problem, especially in Asia ( Megahed et al, 2020 ). Increasing attention has been paid to the relationship between HBV infection and hepatic lipid metabolism recently.…”

Section: Introductionmentioning

confidence: 99%

Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

et al. 2021

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Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.

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“…Chronic HBV infection is a global public health threat; millions of people suffer chronic infection with the virus (1). Previous studies have shown that HBV behaved like a "stealth" virus that establishes persistent infection in hepatocytes (16)(17)(18). Whether or not HBV stimulates and interferes with innate immune responses has been a matter of controversy.…”

Section: Discussionmentioning

confidence: 99%

“…HBV behaves like a "stealth" virus that establishes persistent infection in hepatocytes using multiple evasion strategies to suppress host innate and adaptive immune systems (16)(17)(18). Almost all HBV proteins interfere with intracellular signal transduction pathways, such as IFN associated signaling pathways and inflammation-related pathways (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex

Deng

Cheng

et al. 2021

Front. Immunol.

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Chronic hepatitis B is a major health problem worldwide, with more than 250 million chronic carriers. Hepatitis B virus interferes with the host innate immune system so as to evade elimination via almost all of its constituent proteins; nevertheless, the function of HBsAg with respect to immune escape remains unclear. This study aimed to determine the role HBsAg plays in assisting HBV to escape from immune responses. We found that HBsAg suppressed the activation of the nuclear factor kappa B (NF-кB) pathway, leading to downregulation of innate immune responses. HBsAg interacted with TAK1 and TAB2 specifically, inhibiting the phosphorylation and polyubiquitination of TAK1 and the K63-linked polyubiquitination of TAB2. Autophagy is a major catabolic process participating in many cellular processes, including the life cycle of HBV. We found that HBsAg promoted the autophagic degradation of TAK1 and TAB2 via the formation of complexes with TAK1 and TAB2, resulting in suppression of the NF-κB pathway. The expression of TAK1, TAB2, and the translocation of NF-κB inversely correlated with HBsAg levels in clinical liver tissues. Taken together, our findings suggest a novel mechanism by which HBsAg interacts with TAK1-TAB2 complex and suppresses the activation of NF-κB signaling pathway via reduction of the post-translational modifications and autophagic degradation.

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The Interactions Between HBV and the Innate Immunity of Hepatocytes

Cited by 60 publications

References 93 publications

Role of Mitochondria in Viral Infections

Role of Mitochondria in Viral Infections

Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex

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