A I131V Substitution in the Fusion Glycoprotein of Human Parainfluenza Virus Type 1 Enhances Syncytium Formation and Virus Growth

• Published in: Biological & pharmaceutical bulletin Vol. 42; no. 5; pp. 827 - 832
• Main Authors: Fukushima, Keijo, Takahashi, Tadanobu, Takaguchi, Masahiro, Ito, Seigo, Suzuki, Chihiro, Agarikuchi, Takashi, Kurebayashi, Yuuki, Minami, Akira, Suzuki, Takashi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.05.2019; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Amino acid substitution; Cell fusion; cell-to-cell direct transmission; Exo-a-sialidase; fusion glycoprotein; Fusion protein; Glycoproteins; Hemagglutinins; human parainfluenza virus type 1; Membrane fusion; Membrane proteins; Parainfluenza; Spike glycoprotein; syncytium formation; virus growth; Viruses; fusion glycoprotein; syncytium formation; cell-to-cell direct transmission; human parainfluenza virus type 1; virus growth
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00714

Human parainfluenza virus type 1 (hPIV1) has two spike glycoproteins, the hemagglutinin-neuraminidase (HN) glycoprotein as a receptor-binding protein and the fusion (F) glycoprotein as a membrane-fusion protein. The F glycoprotein mediates both membrane fusion between the virus and cell and membrane fusion between cells, called syncytium formation. Wild-type C35 strain (WT) of hPIV1 shows little syncytium formation of infected cells during virus growth. In the present study, we isolated a variant virus (Vr) from the WT that showed enhanced syncytium formation of infected cells by using our previously established hPIV1 plaque formation assay. Vr formed a larger focus and showed increased virus growth compared with WT. Sequence analysis of the spike glycoprotein genes showed that the Vr had a single amino acid substitution of Ile to Val at position 131 in the fusion peptide region of the F glycoprotein without any substitutions of the HN glycoprotein. The Vr F glycoprotein showed enhanced syncytium formation in F and HN glycoprotein-expressing cells. Additionally, expression of the Vr F glycoprotein increased the focus area of the WT-infected cells. The single amino acid substitution at position 131 in the F glycoprotein of hPIV1 gives hPIV1 abilities to enhance syncytium formation and increase cell-to-cell spread. The present study supports the possibility that hPIV1 acquires increased virus growth in vitro from promotion of direct cell-to-cell transmission by syncytium formation.