HBV特異性T細胞功能的代謝調節

StephenW

Metabolic regulation of the HBV-specific T cell function
Valeria Barili  1 , Carolina Boni  2 , Marzia Rossi  1 , Andrea Vecchi  2 , Alessandra Zecca  2 , Amalia Penna  2 , Gabriele Missale  1 , Carlo Ferrari  3 , Paola Fisicaro  1
Affiliations
Affiliations

    1
    Department of Medicine and Surgery, University of Parma, Parma, Italy; Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
    2
    Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
    3
    Department of Medicine and Surgery, University of Parma, Parma, Italy; Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. Electronic address: [email protected].

    PMID: 33248194 DOI: 10.1016/j.antiviral.2020.104989

Abstract

Chronically HBV infected subjects are more than 260 million worldwide; cirrhosis and liver cancer represent possible outcomes which affect around 700,000 patients per year. Both innate and adaptive immune responses are necessary for viral control and both have been shown to be defective in chronic patients. Metabolic remodeling is an essential process in T cell biology, particularly for T cell activation, differentiation and survival. Cellular metabolism relies on the conversion of nutrients into energy to support intracellular processes, and to generate fundamental intermediate components for cell proliferation and growth. Adaptive immune responses are the central mechanisms for the resolution of primary human infections leading to the activation of pathogen-specific B and T cell functions. In chronic HBV infection the anti-viral immune response fails to contain the virus and leads to persistent hepatic tissue damage which may finally result in liver cirrhosis and cancer. This T cell failure is associated with metabolic alterations suggesting that control of nutrient uptake and intracellular utilization as well as correct regulation of intracellular metabolic pathways are strategic for T cell differentiation during persistent chronic infections. This review will discuss some of the main features of the T cell metabolic processes which are relevant to the generation of an efficient antiviral response, with specific focus on their clinical relevance in chronic HBV infection in the perspective of possible strategies to correct deregulated metabolic pathways underlying T cell dysfunction of chronic HBV patients.

Keywords: CD8+ T cell exhaustion; CD8+ T cell metabolism; Hepatitis B virus; adaptive immunity; chronic HBV infection; metabolic restoration.

Copyright © 2020. Published by Elsevier B.V.

StephenW

HBV特異性T細胞功能的代謝調節
瓦萊里亞·巴里利1（Valeria Barili）1，卡羅萊納州Boni 2，瑪莎婭·羅西（Marzia Rossi）1，安德里亞·韋基（Andrea Vecchi）2，亞歷山德拉·澤卡（Alessandra Zecca）2，阿瑪莉亞·佩納（Amalia Penna）2，加布里埃萊·米薩爾（Gabriele Missale）1，卡羅·法拉利3（Carlo Ferrari）3，保拉·費西卡羅（Paola Fisicaro）1
隸屬關係
隸屬關係

    1個
    意大利帕爾馬大學帕爾馬大學醫學與外科系；意大利帕爾馬省Azienda Ospedaliero-Universitaria di Parma病毒性免疫病理學實驗室，傳染病和肝病學部門。
    2
    意大利帕爾馬省Azienda Ospedaliero-Universitaria di Parma病毒性免疫病理學實驗室，傳染病和肝病學部門。
    3
    意大利帕爾馬大學帕爾馬大學醫學與外科系；意大利帕爾馬省Azienda Ospedaliero-Universitaria di Parma病毒性免疫病理學實驗室，傳染病和肝病學部門。電子地址：[email protected]。

    PMID：33248194 DOI：10.1016 / j.antiviral.2020.104989

抽象

慢性HBV感染的受試者在全球超過2.6億；肝硬化和肝癌代表可能的結果，每年影響約700,000名患者。先天性和適應性免疫應答都是控制病毒所必需的，並且在慢性患者中都顯示出缺陷。代謝重塑是T細胞生物學中必不可少的過程，特別是對於T細胞活化，分化和存活。細胞代謝依賴於營養物質轉化為能量以支持細胞內過程，並產生細胞增殖和生長的基本中間成分。適應性免疫應答是解決原發性人類感染（導致病原體特異性B和T細胞功能激活）的主要機制。在慢性HBV感染中，抗病毒免疫反應無法控制病毒，並導致持續的肝組織損傷，最終可能導致肝硬化和癌症。這種T細胞衰竭與代謝改變有關，表明營養素的攝取和細胞內利用的控制以及細胞內代謝途徑的正確調節對於持續性慢性感染期間T細胞分化具有戰略意義。這篇綜述將討論與有效抗病毒反應的產生相關的T細胞代謝過程的一些主要特徵，並從糾正潛在失調的代謝途徑的可能策略的角度，著重於其與慢性HBV感染的臨床相關性。慢性HBV患者的T細胞功能障礙。

關鍵詞：CD8 + T細胞衰竭CD8 + T細胞代謝；乙型肝炎病毒;適應性免疫慢性乙肝病毒感染；代謝恢復。

版權所有©2020。由Elsevier B.V.發布。

StephenW

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