Sindbis viral structural protein cytotoxicity on human neuroblastoma cells.

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, SH-SY5Y, 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.

• Authors: Eriko Y Saito, Kengo Saito, Tomoro Hishiki, Ayako Takenouchi, Takeshi Saito, Yoshiharu Sato, Keita Terui, Tadashi Matsunaga, Hiroshi Shirasawa, Hideo Yoshida
• Journal: Pediatric surgery international (Pediatr Surg Int) Vol. 36 Issue 10 Pg. 1173-1180 (Oct 2020) ISSN: 1437-9813 [Electronic] Germany
• PMID: 32696122 (Publication Type: Journal Article)

Chemical References

• Viral Structural Proteins

Topics

• Apoptosis (drug effects)
• Fibroblasts (pathology)
• Humans
• Neuroblastoma (pathology, therapy)
• Oncolytic Virotherapy (methods)
• Sindbis Virus
• Tumor Cells, Cultured
• Viral Structural Proteins (therapeutic use)