Detailed analysis of low temperature inactivation of respiratory syncytial virus

• Published in: Scientific reports Vol. 14; no. 1; p. 11823
• Main Authors: Kitai, Yuki, Watanabe, Oshi, Ohmiya, Suguru, Kisu, Tomoko, Ota, Reiko, Kawakami, Kazuyoshi, Katoh, Hiroshi, Fukuzawa, Kaori, Takeda, Makoto, Nishimura, Hidekazu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/596; 631/326/596/2116; 631/326/596/2148; Amino acid substitution; Amino acids; Animals; Cell membranes; Cold Temperature; F protein; Fusion protein; Humanities and Social Sciences; Humans; Inactivation; Infectivity; Low temperature; Membrane fusion; multidisciplinary; Proteins; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Human - physiology; Respiratory Syncytial Viruses; Science; Science (multidisciplinary); Viral Fusion Proteins - chemistry; Viral Fusion Proteins - genetics; Viral Fusion Proteins - metabolism; Virus Inactivation; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-62658-z

Our previous findings indicated that many respiratory syncytial virus (RSV) isolates are unstable at 4 °C compared to 20 °C. Some of the strains completely lose infectivity after 24 h at 4 °C. This study analyzed the inactivation process at 4 °C using a representative strain, RSV/Sendai/851/13. After 24 h of storage at 4 °C, the virus was completely inactivated but retained its ability to attach to and to be taken into host cells. It suggested a reduced fusion ability between the viral and cellular membranes. During storage at 4 °C, the RSV fusion (F) protein underwent a conformational change and was no longer recognized by pre-fusion form-specific antibodies. When the RSV/Sendai/851/13 strain was passaged at 4 °C, a variant with an amino acid substitution, I148T, in the F protein fusion peptide was selected. Also, an amino acid change in G protein demonstrating stability at low temperatures was obtained. These results show that the inactivation of RSV at 4 °C is due to the loss of membrane fusion activity in the F protein, which cannot maintain its pre-fusion state at 4 °C.