2. Academic Validation
  3. CD30 stimulation induces multinucleation and chromosomal instability in HTLV-1-infected cell lines

CD30 stimulation induces multinucleation and chromosomal instability in HTLV-1-infected cell lines

  • Int J Hematol. 2023 Apr 4. doi: 10.1007/s12185-023-03583-1.
Mariko Watanabe 1,  Hiromi Hatsuse 2,  Kazuaki Nagao 2,  Yuetsu Tanaka 3,  Toshiki Watanabe 4,  Ryouichi Horie 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Molecular Genetics, School of Medicine, Kitasato University, 1-15-1 Minami-Ku, Kitasato, Sagamihara, Kanagawa, 252-0374, Japan.
  • 3 School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-Cho, Okinawa, 903-0125, Japan.
  • 4 Laboratory of Practical Management of Medical Information, Graduate School of Medicine, St. Marianna University, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
  • 5 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. [email protected].
PMID: 37014603 DOI: 10.1007/s12185-023-03583-1
Abstract

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.

Keywords

CD30; Chromosomal instability; HTLV-1; ROS; Tax.

Figures
Products