title: A single amino acid mutation at position 170 of human parainfluenza virus type 1 fusion glycoprotein induces obvious syncytium formation and caspase-3-dependent cell death.
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.
authors.affiliation: Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Shizuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takaguchi
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Chika
authors.initials: C
authors.lastname: Hosokawa
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ueyama
authors.forename: Keijo
authors.initials: K
authors.lastname: Fukushima
authors.forename: Takuya
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D002472:Cell Transformation, Viral; D015726:Giant Cells / Q000502:physiology; D015707:HN Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D010222:Parainfluenza Virus 1, Human / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D015707:HN Protein; D014760:Viral Fusion Proteins; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D053148:Caspase 3; D019158:N-Acetylneuraminic Acid