Glutaminolysis of CD4⁺ T Cells: A Potential Therapeutic Target in Viral Diseases

Abstract

CD4⁺ T cells play a critical role in the pathogenesis of viral diseases, which are activated by the internal metabolic pathways encountering with viral antigens. Glutaminolysis converts glutamine into tricarboxylic acid (TCA) circulating metabolites by α-ketoglutaric acid, which is essential for the proliferation and differentiation of CD4⁺ T cells and plays a central role in providing the energy and structural components needed for viral replication after the virus hijacks the host cell. Changes in glutaminolysis in CD4⁺ T cells are accompanied by changes in the viral status of the host cell due to competition for glutamine between immune cells and host cells. More recently, attempts have been made to treat tumours, autoimmune diseases, and viral diseases by altering the breakdown of glutamine in T cells. In this review, we will discuss the current knowledge of glutaminolysis in the CD4⁺ T cell subsets from viral diseases, not only increasing our understanding of immunometabolism but also providing a new perspective for therapeutic target in viral diseases.

Keywords:

• CD4⁺ T cells
• viral diseases
• glutamine
• glutaminolysis
• immune response

Data Sharing Statement

Enquiries about data availability should be directed to the corresponding author.

Acknowledgments

Thanks for the reviewers for their helpful comments on this paper, and thank American Journal Experts (AJE) for English language editing.

Disclosure

The authors have no relevant financial or non-financial interests to disclose in this work.

Additional information

Funding

This research was supported by Zhejiang Provincial Key Research and Development Program grant number 2020C03032, Zhejiang Provincial Natural Science Foundation of China grant number LQ20H080002, and the National Natural Science Foundation of China grant number 82172335, 81971994, 81871709 and 91846103.