Conflicting effects of poly(ADP-ribose) polymerase inhibitor on cell-mediated and virion-mediated HTLV-1 infection

Masakazu Tanaka; Koji Tanaka; Chieri Ida; Atsushi Oue; Sachiko Yamashita; Jinchun Yao; Norihiro Takenouchi; Masanao Miwa

doi:10.1016/j.virusres.2019.197653

Conflicting effects of poly(ADP-ribose) polymerase inhibitor on cell-mediated and virion-mediated HTLV-1 infection

Virus Res. 2019 Sep:270:197653. doi: 10.1016/j.virusres.2019.197653. Epub 2019 Jul 9.

Authors

Masakazu Tanaka¹, Koji Tanaka², Chieri Ida³, Atsushi Oue⁴, Sachiko Yamashita⁵, Jinchun Yao⁶, Norihiro Takenouchi⁶, Masanao Miwa⁷

Affiliations

¹ Department of Microbiology, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan; Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Kagoshima 890-8544, Japan. Electronic address: tanakam@m.kufm.kagoshima-u.ac.jp.
² Department of Microbiology, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan; Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan.
³ Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan; College of Nagoya Women's University, Nagoya, Aichi, 467-8610, Japan.
⁴ Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
⁵ Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan.
⁶ Department of Microbiology, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan.
⁷ Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan; Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.

PMID: 31299194
DOI: 10.1016/j.virusres.2019.197653

Abstract

Adult T-cell leukemia and human T-cell leukemia virus type 1 (HTLV-1) - associated myelopathy/tropical spastic paraparesis, which develop after HTLV-1 infection, are difficult to cure. In particular, the mode of HTLV-1 propagation is not well understood. Poly (ADP-ribose) polymerase-1 is reported to be a co-activator of HTLV-1 Tax protein; however, the effects of polyADP-ribosylation on infectivity of HTLV-1 have not been fully clarified. We studied the effects of a PARP inhibitor on two modes of HTLV-1 transmission: through cell adhesion between MT-2 cells (an HTLV-1-infected cell line) and uninfected cells and through virus particles produced by HTLV-1-producing c77 cells. Although the PARP inhibitor decreased HTLV-1 infection through cell adhesion, it increased HTLV-1 infection through virion production and caused apoptosis of HTLV-1-infected cells. Thus, careful consideration is required for clinical application of PARP inhibitors in HTLV-1 patients.

Keywords: HTLV-1; PARP inhibitor; Poly ADP ribosylation; Viral infectivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Human T-lymphotropic virus 1 / drug effects*
Human T-lymphotropic virus 1 / physiology
Humans
Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
T-Lymphocytes / drug effects
T-Lymphocytes / virology
Virion / drug effects*
Virus Attachment / drug effects*

Substances

Poly(ADP-ribose) Polymerase Inhibitors