Sindbis viral structural protein cytotoxicity on human neuroblastoma cells
- PDF / 1,310,561 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 65 Downloads / 179 Views
ORIGINAL ARTICLE
Sindbis viral structural protein cytotoxicity on human neuroblastoma cells Eriko Y. Saito1 · Kengo Saito2 · Tomoro Hishiki1 · Ayako Takenouchi1 · Takeshi Saito2 · Yoshiharu Sato1 · Keita Terui1 · Tadashi Matsunaga1 · Hiroshi Shirasawa2 · Hideo Yoshida1 Accepted: 14 July 2020 © The Author(s) 2020
Abstract Purpose Oncolytic viral therapy for neuroblastoma (NB) cells with Sindbis virus (SINV) is a promising strategy for treating high-risk NB. Here, we evaluated the possibility of using SINV structural proteins as therapeutic agents for NB since UV-inactivated SINV could induce cytopathogenic effects. Methods The cytotoxicity of UV-inactivated SINV toward human NB cell lines NB69, NGP, GOTO, NLF, SK-N-SH, SHSY5Y, CHP134, NB-1, IMR32, and RT-BM-1 were analyzed. Apoptosis was confirmed by TUNEL assays. To determine the components of SINV responsible for the cytotoxicity of UV-inactivated SINV, expression vectors encoding the structural proteins, namely capsid, E2, and E1, were transfected in NB cells. Cytotoxicity was evaluated by MTT assays. Results UV-inactivated SINV elicited more significant cytotoxicity in NB69, NGP, and RT-BM-1 than in normal human fibroblasts. Results of the transfection experiments showed that all NB cell lines susceptible to UV-inactivated SINV were highly susceptible to the E1 protein, whereas fibroblasts transfected with vectors harboring capsid, E1, or E2 were not. Conclusions We demonstrated that the cytotoxicity of the UV-inactivated SINV is due to apoptosis induced by the E1 structural protein of SINV, which can be used selectively as a therapeutic agent for NB. Keywords Apoptosis · E1 · Neuroblastoma · UV · Sindbis virus
Introduction Neuroblastoma (NB) is the most common solid extracranial tumor of early childhood [1, 2]. NB patients with highrisk disease continue to exhibit poor prognosis even after intensive chemotherapy and autologous bone marrow transplantation [3–5], which limits their treatment options. The resistance of NBs to conventional therapies has prompted the search for a novel therapeutic approach based on the naturally occurring oncolytic virus, Sindbis virus (SINV). Previously, we have reported that the SINV AR339 strain may be used as a novel therapeutic agent for human cervical, ovarian, and oral cancer [6–8]. Human NB cells and NB * Hiroshi Shirasawa [email protected]‑u.jp 1
Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1‑8‑1 Inohana, Chuou‑ku, Chiba 260‑8670, Japan
Molecular Virology, Graduate School of Medicine, Chiba University, 1‑8‑1 Inohana, Chuou‑ku, Chiba 260‑8670, Japan
2
xenograft tumors are also susceptible to replication-competent SINV [9]. SINV, a mosquito-borne alphavirus, is an enveloped, plus-strand RNA virus that causes infection of neurons and age-dependent encephalomyelitis in mice, and mild mosquito-borne viral arthritis in humans [10]. Neurons are the primary targets for SINV infection in the central nervous system (CNS), and both host and viral factors determine the fate of
Data Loading...
