Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein
Muhammad Nabeel Amjad,
Jing Wang,
Muhammad Awais Ashraf,
Bei Shen,
Ghayyas ud Din,
Muhammad Asif Raza,
Muhammad Shoaib,
Lihuan Yue,
Lingdie Chen,
Huiting Xu,
Wei Dong,
Yihong Hu
Affiliations
Muhammad Nabeel Amjad
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China
Jing Wang
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China
Muhammad Awais Ashraf
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China
Bei Shen
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China
Ghayyas ud Din
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China
Muhammad Asif Raza
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China
Muhammad Shoaib
Key Laboratory of New Animal Drug Project, Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, China
Lihuan Yue
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China
Lingdie Chen
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China
Huiting Xu
Pediatric Department, Nanxiang Branch of Ruijin Hospital, Shanghai, 201802, China
Wei Dong
Pediatric Department, Nanxiang Branch of Ruijin Hospital, Shanghai, 201802, China
Yihong Hu
CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang Road 320, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China; Corresponding author. CAS Key Laboratory of Molecular Virology & Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Yueyang road 320, Shanghai, 200031, China.
Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.
