Authors: Takaguchi, Masahiro¹; Takahashi, Tadanobu¹; Hosokawa, Chika¹; Ueyama, Hiroo¹; Fukushima, Keijo¹; Hayakawa, Takuya¹; Itoh, Kazuhiko¹; Ikeda, Kiyoshi²; Suzuki, Takashi¹

Source: The Journal of Biochemistry, Volume 149, Number 2, 20 February 2011 , pp. 191-202(12)

Publisher: Oxford University Press

Abstract:

An escape mutant of human parainfluenza virus type 1 (hPIV1), which was selected by serial passage in the presence of a sialidase inhibitor, 4-O-thiocarbamoylmethyl-2-deoxy-2,3-didehydro-N-acetylneur-aminic acid (TCM-Neu5Ac2en), exhibited remarkable syncytium formation and virus-induced cell death in LLC-MK2 cells but no difference in susceptibility for the sialidase inhibitor TCM-Neu5Ac2en from that of wild-type hPIV1 strain C35 (WT). The mutant virus also had higher replication and plaque formation abilities. The mutant virus acquired two amino acid mutations, Glu to Gly at position 170 and Ala to Glu 442 in fusion (F) glycoprotein, but no mutations in haemaggulutinin-neuraminidase (HN) glycoprotein. Using cells co-expressing F and HN genes with site-specific mutagenesis, we demonstrated that a point mutation of Glu to Gly at position 170, which was estimated to be located in hPIV1 F glycoprotein heptad repeat 1, was required for obvious syncytium formation and caspase-3-dependent cell death. In contrast, wild-type F glycoprotein induced no synctium formation or cell death. The findings suggest that a single amino acid mutation of hPIV1 F glycoprotein promotes syncytium formation that is followed by caspase-3-dependent cell death.

Keywords: Fusion protein; heptad repeat; human parainfluenza virus; membrane fusion; sialidase inhibitor

Document Type: Regular paper

DOI: http://dx.doi.org/10.1093/jb/mvq139

Affiliations: 1: Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and Global COE Program for Innovation in Human Health Sciences, Shizuoka 422-8526 and , 2: Department of Organic Chemistry, Faculty of Pharmaceutical Sciences, Hiroshima International University, Hiroshima 737-0112, Japan,

Publication date: 2011-02-20

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