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Molecular Mechanisms of Severe Diseases Caused by Epstein-Barr Virus Infection

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Abstract

Purpose of Review

Epstein-Barr virus (EBV) is a ubiquitous virus that infects > 90% of individuals. EBV has been linked to severe conditions such as chronic active EBV disease (CAEBV) and hemophagocytic lymphohistiocytosis (HLH), which are related to the proliferation of EBV-infected T or natural killer (NK) cells. CAEBV and EBV-HLH are life-threatening illnesses, and treatment strategies for these diseases have not been fully established. This review focuses on the clinical aspects and pathogenesis of CAEBV and EBV-HLH.

Recent Findings

In patients with CAEBV, somatic driver mutations, including DDX3X and other malignancy-related genes, are frequently observed in EBV-infected T/NK cells. Therefore, CAEBV lymphomagenesis may be related to the serial acquisition of somatic mutations in T/NK cells. Furthermore, intragenic deletions in the EBV genes, which are related to lytic infections, are frequently observed in CAEBV.

EBV can trigger HLH in healthy individuals, and various EBV-susceptible primary immunodeficiencies have been discovered. In EBV-HLH, cytotoxic T cells and macrophages become activated and secrete excessive amounts of cytokines, which is known as a “cytokine storm.” Abnormally high expression levels of active markers were observed in macrophages and CD8 + T cells at the single-cell level.

Summary

Accumulating evidence suggests that systemic inflammation, accompanied by clonal proliferation of EBV-infected T or NK cells, is involved in the pathogenesis of CAEBV and EBV-HLH. Understanding the disease pathogenesis is important for the development of new treatment strategies.

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  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Jun-ichi Kawada

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Kawada, Ji. Molecular Mechanisms of Severe Diseases Caused by Epstein-Barr Virus Infection. Curr Clin Micro Rpt 10, 206–213 (2023). https://doi.org/10.1007/s40588-023-00203-8

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