Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G protein. In the present study, the effect of amino acid substitution on the structure and stability of the ectodomain G protein was studied. Further, it was investigated whether mutation (K117A) in the CX3C motif of G protein alters the binding with heparan sulfate. The point mutation significantly affects the conformational stability of the G protein. The mutant protein showed a low binding affinity with heparan sulfate as compared to the wild-type G protein, as determined by fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking studies. The low binding affinity and decreased stability suggested that this mutation may play an important role in prevention of attachment of virion to the host cell receptors. Collectively, this investigation suggests that mutation in the CX3C motif of G protein may likely improve the efficacy and safety of the RSV vaccine.
Highlights
Published: 9 February 2022Respiratory syncytial virus (RSV), which belongs to the family Pneumoviridae and genusOrthopneumovirus, is the leading cause of acute lower respiratory infection in the elderly and children, especially those less than 2 years of age [1,2,3]
Previous studies showed that the basic amino acids of the heparin-binding domain (HBD) of the G protein helps in the attachment of RSV through negatively charged heparan sulfate present on the host cells [16,19]
Previous studies showed that the CX3C chemokine motif present in the central conserved region of G protein bound with the CX3CR1 receptor present on human airway epithelial (HAE) cells [16]
Summary
Respiratory syncytial virus (RSV), which belongs to the family Pneumoviridae and genus. Previous studies showed that the basic amino acids of the HBD of the G protein helps in the attachment of RSV through negatively charged heparan sulfate present on the host cells [16,19]. The human mAbs 3G12 and 3D3, which bind with the CCD, have been shown to strongly neutralize both subtypes of RSV These antibodies bind to the G protein of RSV with high affinity, and protected mice from RSV infection [31,32]. Previous studies showed that the T–cell epitope, which is found in amino acids 184–203 in the G protein, is involved in protective immunity against the RSV infection and induction of T-cell response and eosinophilia [35,36]. Bergeron and colleagues reported that a vaccine targeting the RSV G protein encoded with a central conserved domain induced antibodies, blocking the CX3C-CX3CR1 [41]. Isothermal titration calorimetry (ITC), fluorescence quenching, absorbance spectroscopy, and in silico approaches were exploited to determine the interaction of the mutant G protein with the heparan sulfate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
