Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition

Zhou, Li; He, Rui; Fang, Peining; Li, Mengqi; Yu, Haisheng; Wang, Qiming; Yu, Yongsheng; Wang, Xinghuan; Zhang, Yi; Chen, Aidong; Peng, Nanfang; Lin, Yong; Zhang, Rui; Trilling, Mirko; Broering, Ruth; Lu, Mengji; Zhu, Ying; Shi, Lei

doi:10.1038/s41467-020-20316-8

Cited by 100 publications

(98 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, HBV can help the virus evade innate immune recognition by activating glycolysis, promoting HK activity and lactic acid production, and blocking RLR signaling by inhibiting RIG-I/MAVS interactions. 117 In livers with chronic HBV infection, amino acid depletion affects protein and nucleotide synthesis in T cells, which in turn affects the activation and function of these cells. 118 This may be an important mechanism that promotes the progression of HBV-associated HCC.…”

Section: Hbv and Metabolismmentioning

confidence: 99%

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

Yu¹,

Han²,

Zhao³

et al. 2021

JHC

137

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a common malignancy, and the hepatitis B virus (HBV) is its major pathogenic factor. Over the past decades, it has been confirmed that HBV infection could promote disease progression through a variety of mechanisms, ultimately leading to the malignant transformation of liver cells. Many factors have been identified in the pathogenesis of HBV-associated HCC (HBV-HCC), including HBV gene integration, genomic instability caused by mutation, and activation of cancer-promoting signaling pathways. As research in the progression of HBV-HCC progresses, the role of many new mechanisms, such as epigenetics, exosomes, autophagy, metabolic regulation, and immune suppression, is also being continuously explored. The occurrence of HBV-HCC is a complex process caused by interactions across multiple genes and multiple steps, where the synergistic effects of various cancer-promoting mechanisms accelerate the process of disease evolution from inflammation to tumorigenesis. In this review, we aim to provide a brief overview of the mechanisms involved in the occurrence and development of HBV-HCC, which may contribute to a better understanding of the role of HBV in the occurrence and development of HCC.

show abstract

Section: Hbv and Metabolismmentioning

confidence: 99%

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

Yu¹,

Han²,

Zhao³

et al. 2021

JHC

137

View full text Add to dashboard Cite

show abstract

“…Although it remains controversial whether the host could detect the virion and express innate and IFN genes during HBV infection (20,21,(93)(94)(95)(96)(97), HBV has developed strategies to counteract the innate and IFN system. HBV particles readily inhibit host innate immune responses upon virion/cell interaction (98,99). HBV polymerase (Pol) and HBx could block multiple critical innate immune response pathways in hepatocytes, including RIG-I, STING, TRIM22, and IRF (64,65,100).…”

Section: Viral Factorsmentioning

confidence: 99%

Interferon and Hepatitis B: Current and Future Perspectives

Chen

2021

Front. Immunol.

109

View full text Add to dashboard Cite

Chronic hepatitis B virus (HBV) infection remains a major health burden worldwide for which there is still no effective curative treatment. Interferon (IFN) consists of a group of cytokines with antiviral activity and immunoregulatory and antitumor effects, that play crucial roles in both innate and adaptive immune responses. IFN-α and its pegylated form have been used for over thirty years to treat chronic hepatitis B (CHB) with advantages of finite treatment duration and sustained virologic response, however, the efficacy is limited and side effects are common. Here, we summarize the status and unique advantages of IFN therapy against CHB, review the mechanisms of IFN-α action and factors affecting IFN response, and discuss the possible improvement of IFN-based therapy and the rationale of combinations with other antiviral agents in seeking an HBV cure.

show abstract

“…Furthermore, MAVS activation leads to the dissociation and inactivation of HK2, which further decreases lactate levels ( Zhang et al, 2019 ). Interestingly, similar to many cancer cells, virally infected cells shift their metabolism to aerobic glycolysis ( DeBerardinis and Chandel, 2020 ; Zhou et al, 2021 ) and increase the production of lactate, which may be considered as an evolving mechanism employed by viruses to evade immune surveillance.…”

Section: Mitochondrial Innate Immune Signalling During Infectionmentioning

confidence: 99%

Metabolism and Innate Immunity Meet at the Mitochondria

Bahat

MacVicar

Langer

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mitochondria are master regulators of metabolism and have emerged as key signalling organelles of the innate immune system. Each mitochondrion harbours potent agonists of inflammation, including mitochondrial DNA (mtDNA), which are normally shielded from the rest of the cell and extracellular environment and therefore do not elicit detrimental inflammatory cascades. Mitochondrial damage and dysfunction can lead to the cytosolic and extracellular exposure of mtDNA, which triggers inflammation in a number of diseases including autoimmune neurodegenerative disorders. However, recent research has revealed that the extra-mitochondrial exposure of mtDNA is not solely a negative consequence of mitochondrial damage and pointed to an active role of mitochondria in innate immunity. Metabolic cues including nucleotide imbalance can stimulate the release of mtDNA from mitochondria in order to drive a type I interferon response. Moreover, important effectors of the innate immune response to pathogen infection, such as the mitochondrial antiviral signalling protein (MAVS), are located at the mitochondrial surface and modulated by the cellular metabolic status and mitochondrial dynamics. In this review, we explore how and why metabolism and innate immunity converge at the mitochondria and describe how mitochondria orchestrate innate immune signalling pathways in different metabolic scenarios. Understanding how cellular metabolism and metabolic programming of mitochondria are translated into innate immune responses bears relevance to a broad range of human diseases including cancer.

show abstract

Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition

Cited by 100 publications

References 50 publications

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

Interferon and Hepatitis B: Current and Future Perspectives

Metabolism and Innate Immunity Meet at the Mitochondria

Contact Info

Product

Resources

About