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

doi:10.3390/v14112382

Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico

Viruses. 2022 Oct 28;14(11):2382. doi: 10.3390/v14112382.

Authors

Mao Akagawa¹, Tatsuya Shirai², Mitsuru Sada¹, Norika Nagasawa¹, Mayumi Kondo³, Makoto Takeda⁴, Koo Nagasawa⁵, Ryusuke Kimura^{2

6}, Kaori Okayama¹, Yuriko Hayashi¹, Toshiyuki Sugai⁷, Takeshi Tsugawa⁸, Haruyuki Ishii⁹, Hisashi Kawashima¹⁰, Kazuhiko Katayama¹¹, Akihide Ryo¹², Hirokazu Kimura^{1

2}

Affiliations

¹ Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Japan.
² Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa-shi 377-0008, Japan.
³ Department of Clinical Engineering, Faculty of Medical Technology, Gunma Paz University, Takasaki-shi 370-0006, Japan.
⁴ Department of Virology III, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011, Japan.
⁵ Department of Pediatrics, Graduate School of Medical Science, Chiba University, Chiba-shi 260-8670, Japan.
⁶ Department of Bacteriology, Graduate School of Medicine, Gunma University, Maebashi-shi 371-8514, Japan.
⁷ Department of Nursing Science, Graduate School of Health Science, Hiroshima University, Hiroshima-shi 734-8551, Japan.
⁸ Department of Pediatrics, School of Medicine, Sapporo Medical University, Sapporo-shi 060-8543, Japan.
⁹ Department of Respiratory Medicine, School of Medicine, Kyorin University, Mitaka-shi, Tokyo 181-8611, Japan.
¹⁰ Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan.
¹¹ Laboratory of Viral Infection Control, Graduate School of Infection Control Sciences, Ōmura Satoshi Memorial Institute, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
¹² Department of Microbiology, School of Medicine, Yokohama City University, Yokohama-shi 236-0004, Japan.

Abstract

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.

Keywords: Toll-like receptor 4; docking simulation; in silico; myeloid differentiation factor-2; respiratory syncytial virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
Antibodies, Neutralizing
Antibodies, Viral
Binding Sites, Antibody
Humans
Protein Binding
Respiratory Syncytial Virus Infections*
Respiratory Syncytial Virus, Human*
Toll-Like Receptor 4 / metabolism
Viral Fusion Proteins

Substances

Antibodies, Neutralizing
Antibodies, Viral
TLR4 protein, human
Toll-Like Receptor 4
Viral Fusion Proteins
ATP Binding Cassette Transporter, Subfamily B

Grants and funding

This research was supported by Japan Agency for Medical Research and Development, AMED (https://www.amed.go.jp/, accessed on 1 April 2022) under Grant Number JP22fk0108119. The funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation.