Division of Hematology, Department of Laboratory Sciences, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0373, Japan.
Department of Molecular Genetics, School of Medicine, Kitasato University, 1-15-1 Minami-Ku, Kitasato, Sagamihara, Kanagawa, 252-0374, Japan.
Int J Hematol. 2023 Jul;118(1):75-87. doi: 10.1007/s12185-023-03583-1. Epub 2023 Apr 4.
A recent report indicated involvement of CD30 in progression of human leukemia virus type 1 (HTLV-1) infection, but the exact roles of CD30 in this process remain unclear. This study was conducted to determine the role of CD30 by stimulating CD30 expressed on HTLV-1-infected cell lines with CD30 ligand and observing its effects. CD30 stimulation increased multinucleated cells and inhibited proliferation of HTLV-1-infected cells. This inhibition was recovered by interruption of CD30 stimulation. Chromatin bridges found in multinucleated cells suggested DNA damage. CD30 stimulation triggered DNA double-strand breaks (DSBs) and chromosomal imbalances. CD30 stimulation induced reactive oxygen species (ROS), which induced DSBs. Generation of ROS and multinucleated cells by CD30 was dependent on phosphoinositide 3-kinase. RNA sequencing showed that CD30 stimulation produced significant changes in gene expression profiles, including upregulation of programmed death ligand 1 (PD-L1). Tax, which has also been shown to induce multinucleation and chromosomal instability, failed to induce CD30. These results suggest that induction of CD30, independent of Tax, triggers morphological abnormalities, chromosomal instability, and alteration of gene expression in HTLV-1-infected cells.
最近的一份报告表明，CD30 参与了人类 T 细胞白血病病毒 1 型（HTLV-1）感染的进展，但 CD30 在这一过程中的确切作用仍不清楚。本研究通过用 CD30 配体刺激 HTLV-1 感染细胞系上表达的 CD30，观察其作用来确定 CD30 的作用。CD30 刺激增加了多核细胞并抑制了 HTLV-1 感染细胞的增殖。通过中断 CD30 刺激可以恢复这种抑制。在多核细胞中发现的染色质桥表明存在 DNA 损伤。CD30 刺激引发 DNA 双链断裂（DSBs）和染色体失衡。CD30 刺激诱导活性氧（ROS），从而引发 DSBs。ROS 的产生和 CD30 引起的多核细胞依赖于磷酸肌醇 3-激酶。RNA 测序显示，CD30 刺激导致基因表达谱发生显著变化，包括程序性死亡配体 1（PD-L1）的上调。Tax 也已被证明能诱导多核化和染色体不稳定，但不能诱导 CD30。这些结果表明，CD30 的诱导，独立于 Tax，可触发 HTLV-1 感染细胞的形态异常、染色体不稳定和基因表达的改变。
