細胞代謝在控制肝炎病毒中起什麼作用？

StephenW

細胞代謝在控制肝炎病毒中起什麼作用？
Olivier Diaz 1 、Pierre-Olivier Vidalain 1 、Christophe Ramière 1 2 、Vincent Lotteau 1 、Laure Perrin-Cocon 1
隸屬關係
隸屬關係

     1個
     CIRI，國際傳染病研究中心，病毒感染、代謝和免疫團隊，里昂大學，Inserm，U1111，克勞德伯納德里昂大學 1，CNRS，UMR5308，ENS de Lyon，里昂，法國。
     2個
     病毒學實驗室，Hôpital de la Croix-Rousse，Hospices Civils de Lyon，里昂，法國。

     PMID：36466918 PMCID：PMC9713817 DOI：10.3389/fimmu.2022.1033314

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抽象的

乙型、丙型和丁型肝炎病毒（分別為 HBV、HCV、HDV）特異性感染人類肝細胞並經常建立肝臟的慢性病毒感染，從而逃避抗病毒免疫多年。 與其他病毒一樣，肝炎病毒依賴細胞機制來滿足其複制所需的能量和代謝產物。 儘管這最初被認為是被動寄生，但研究表明，肝炎病毒通過與特定酶（例如糖酵解的第一種限速酶——葡萄糖激酶）的分子相互作用，主動重新連接細胞代謝。 作為免疫代謝領域研究工作的一部分，還表明病毒引起的代謝變化可能對先天抗病毒反應產生直接影響。 相反，先天免疫受體檢測到病毒成分不僅會觸發抗病毒防禦的激活，還會誘導深度代謝重編程，這對於支持免疫功能至關重要。 總之，病毒成分、先天免疫和肝細胞代謝之間的這些複雜的三角相互作用可以解釋為什麼慢性肝炎感染會逐漸導致肝臟炎症並進展為肝硬化、纖維化和肝細胞癌 (HCC)。 在這份手稿中，我們首先對先天抗病毒反應與細胞代謝之間的已知聯繫進行了全面概述。 然後，我們報告肝炎病毒干擾肝細胞細胞代謝的已知分子機制，並討論對先天免疫反應的潛在影響。 最後，我們提供的證據表明，靶向肝細胞代謝的藥物可以用作一種創新策略，不僅可以剝奪病毒的關鍵代謝物，還可以恢復清除感染所必需的先天抗病毒反應。

關鍵詞：細胞代謝； 肝炎病毒； 肝細胞； 免疫代謝; 炎; 先天免疫; 肝臟疾病。

版權所有 © 2022 Diaz、Vidalain、Ramière、Lotteau 和 Perrin-Cocon。
利益衝突聲明

作者聲明，該研究是在沒有任何可能被解釋為潛在利益衝突的商業或財務關係的情況下進行的。

StephenW

What role for cellular metabolism in the control of hepatitis viruses?
Olivier Diaz  1 , Pierre-Olivier Vidalain  1 , Christophe Ramière  1   2 , Vincent Lotteau  1 , Laure Perrin-Cocon  1
Affiliations
Affiliations

    1
    CIRI, Centre International de Recherche en Infectiologie, Team VIRal Infection, Metabolism and Immunity, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
    2
    Laboratoire de Virologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.

    PMID: 36466918 PMCID: PMC9713817 DOI: 10.3389/fimmu.2022.1033314

Free PMC article
Abstract

Hepatitis B, C and D viruses (HBV, HCV, HDV, respectively) specifically infect human hepatocytes and often establish chronic viral infections of the liver, thus escaping antiviral immunity for years. Like other viruses, hepatitis viruses rely on the cellular machinery to meet their energy and metabolite requirements for replication. Although this was initially considered passive parasitism, studies have shown that hepatitis viruses actively rewire cellular metabolism through molecular interactions with specific enzymes such as glucokinase, the first rate-limiting enzyme of glycolysis. As part of research efforts in the field of immunometabolism, it has also been shown that metabolic changes induced by viruses could have a direct impact on the innate antiviral response. Conversely, detection of viral components by innate immunity receptors not only triggers the activation of the antiviral defense but also induces in-depth metabolic reprogramming that is essential to support immunological functions. Altogether, these complex triangular interactions between viral components, innate immunity and hepatocyte metabolism may explain why chronic hepatitis infections progressively lead to liver inflammation and progression to cirrhosis, fibrosis and hepatocellular carcinoma (HCC). In this manuscript, we first present a global overview of known connections between the innate antiviral response and cellular metabolism. We then report known molecular mechanisms by which hepatitis viruses interfere with cellular metabolism in hepatocytes and discuss potential consequences on the innate immune response. Finally, we present evidence that drugs targeting hepatocyte metabolism could be used as an innovative strategy not only to deprive viruses of key metabolites, but also to restore the innate antiviral response that is necessary to clear infection.

Keywords: cellular metabolism; hepatitis virus; hepatocyte; immunometabolism; inflammation; innate immunity; liver diseases.

Copyright © 2022 Diaz, Vidalain, Ramière, Lotteau and Perrin-Cocon.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

StephenW

https://www.frontiersin.org/arti ... mu.2022.1033314/pdf