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Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/64333

Title: Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection
Authors: Maeda, Naoyoshi Browse this author →KAKEN DB
Furukawa, Atsushi Browse this author
Kakita, Kosuke Browse this author
Anada, Masahiro Browse this author →KAKEN DB
Hashimoto, Shunichi Browse this author →KAKEN DB
Matsunaga, Shigeki Browse this author →KAKEN DB
Kuroki, Kimiko Browse this author →KAKEN DB
Ose, Toyoyuki Browse this author →KAKEN DB
Kato, Akihisa Browse this author →KAKEN DB
Arii, Jun Browse this author →KAKEN DB
Kawaguchi, Yasushi Browse this author →KAKEN DB
Arase, Hisashi Browse this author →KAKEN DB
Maenaka, Katsumi Browse this author →KAKEN DB
Keywords: cell-based fusion assay
drug screening
herpes simplex virus type 1
paired immunoglobulin-like type 2 receptor alpha
Issue Date: Nov-2016
Publisher: The Pharmaceutical Society of Japan
Journal Title: Biological & pharmaceutical bulletin
Volume: 39
Issue: 11
Start Page: 1897
End Page: 1902
Publisher DOI: 10.1248/bpb.b16-00533
PMID: 27803463
Abstract: Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILR alpha) in vitro. In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. The CHO-K1 cells stably expressing PILRa were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. The effector and target cells were co-cultured, and luminescence was measured when both cells were successfully fused. Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases.
Type: article
URI: http://hdl.handle.net/2115/64333
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 前田 直良

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