Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico
Mao Akagawa,
Tatsuya Shirai,
Mitsuru Sada,
Norika Nagasawa,
Mayumi Kondo,
Makoto Takeda,
Koo Nagasawa,
Ryusuke Kimura,
Kaori Okayama,
Yuriko Hayashi,
Toshiyuki Sugai,
Takeshi Tsugawa,
Haruyuki Ishii,
Hisashi Kawashima,
Kazuhiko Katayama,
Akihide Ryo,
Hirokazu Kimura
Affiliations
Mao Akagawa
Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan
Tatsuya Shirai
Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa-shi 377-0008, Japan
Mitsuru Sada
Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan
Norika Nagasawa
Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan
Mayumi Kondo
Department of Clinical Engineering, Faculty of Medical Technology, Gunma Paz University, Takasaki-shi 370-0006, Japan
Makoto Takeda
Department of Virology III, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011, Japan
Koo Nagasawa
Department of Pediatrics, Graduate School of Medical Science, Chiba University, Chiba-shi 260-8670, Japan
Ryusuke Kimura
Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa-shi 377-0008, Japan
Kaori Okayama
Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan
Yuriko Hayashi
Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan
Toshiyuki Sugai
Department of Nursing Science, Graduate School of Health Science, Hiroshima University, Hiroshima-shi 734-8551, Japan
Takeshi Tsugawa
Department of Pediatrics, School of Medicine, Sapporo Medical University, Sapporo-shi 060-8543, Japan
Haruyuki Ishii
Department of Respiratory Medicine, School of Medicine, Kyorin University, Mitaka-shi, Tokyo 181-8611, Japan
Hisashi Kawashima
Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
Kazuhiko Katayama
Laboratory of Viral Infection Control, Graduate School of Infection Control Sciences, Ōmura Satoshi Memorial Institute, Kitasato University, Minato-ku, Tokyo 108-8641, Japan
Akihide Ryo
Department of Microbiology, School of Medicine, Yokohama City University, Yokohama-shi 236-0004, Japan
Hirokazu Kimura
Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan
Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV.
