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<p>Systemic chronic active Epstein–Barr virus disease (sCAEBV) is an intractable disorder characterized by clonal proliferation of EBV-infected T- and NK-cells, leading to persistent systemic inflammation and progression to hemophagocytic lymphohistiocytosis (HLH). The EBV genome encodes 40 mature microRNAs known as miR-BARTs. The expression of miR-BARTs has been reported in other EBV-positive diseases and is associated with tumorigenesis. In this study, we investigated the expression of miR-BARTs in sCAEBV. Expression of miR-BARTs was highly abundant in 4 sCAEBV-derived EBV-positive T- or NK-cell lines and in EBV-infected T- or NK-cells from 23 sCAEBV patients. The highest expression levels were observed for miR-BART7-3p. Sequence analysis revealed no deletions in the EBV genome encoding miR-BARTs. Inhibition of miR-BART7-3p altered the expression of immune-related genes in sCAEBV-derived cell lines. Abundant miR-BART expression was also observed in patients’ plasma, with miR-BART7-3p showing the highest levels. Notably, miR-BART7-3p expression was detected in macrophages within the spleen of an sCAEBV patient with HLH. These findings suggest that miR-BARTs are highly expressed and secreted by EBV-infected cells in sCAEBV. We hypothesize that secreted miR-BARTs may be taken up by monocytes, potentially regulating their functions and contributing to inflammation in sCAEBV. Further studies are needed to elucidate these mechanisms. </p>

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Expression profiling of Epstein–Barr virus-derived microRNA in systemic chronic active EBV disease

  • 期刊论文

  • 发表日期：

    2025年7月25日

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  • Mayumi Yoshimori,
  • Miwako Nishio,
  • Ayaka Ohashi,
  • Yuri Maekawa,
  • Runa Shimomaki,
  • Morito Kurata,
  • Kotaro Yoshioka,
  • Takanori Yokota,
  • Ryusuke Nabeshima,
  • Ayako Arai

摘要

Systemic chronic active Epstein–Barr virus disease (sCAEBV) is an intractable disorder characterized by clonal proliferation of EBV-infected T- and NK-cells, leading to persistent systemic inflammation and progression to hemophagocytic lymphohistiocytosis (HLH). The EBV genome encodes 40 mature microRNAs known as miR-BARTs. The expression of miR-BARTs has been reported in other EBV-positive diseases and is associated with tumorigenesis. In this study, we investigated the expression of miR-BARTs in sCAEBV. Expression of miR-BARTs was highly abundant in 4 sCAEBV-derived EBV-positive T- or NK-cell lines and in EBV-infected T- or NK-cells from 23 sCAEBV patients. The highest expression levels were observed for miR-BART7-3p. Sequence analysis revealed no deletions in the EBV genome encoding miR-BARTs. Inhibition of miR-BART7-3p altered the expression of immune-related genes in sCAEBV-derived cell lines. Abundant miR-BART expression was also observed in patients’ plasma, with miR-BART7-3p showing the highest levels. Notably, miR-BART7-3p expression was detected in macrophages within the spleen of an sCAEBV patient with HLH. These findings suggest that miR-BARTs are highly expressed and secreted by EBV-infected cells in sCAEBV. We hypothesize that secreted miR-BARTs may be taken up by monocytes, potentially regulating their functions and contributing to inflammation in sCAEBV. Further studies are needed to elucidate these mechanisms.