Functional Features of the Respiratory Syncytial Virus G Protein

Abstract

Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children <5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design.

Parainfluenza virus 5 is a next‐generation vaccine vector for human infectious pathogens

“…RSV is a major cause of pediatric lower respiratory tract infections worldwide, and repeated RSV infections can lead to serious diseases in infants, the elderly, and individuals with compromised immune, cardiac, or pulmonary systems. 117 Recently, Nirsevimab (Beyfortus), a monoclonal antibody targeting RSV, has received regulatory approval in the UK. Nirsevimab could offer newborns and infants immediate prevention against RSV-related lower respiratory tract infection.…”

RSV disease in infants and young children: Can we see a brighter future?

“… 121 , 157 First, as mAbs target-specific epitopes on the RSV F protein, there is the potential for emergence of resistant strains, and this will need to carefully monitored. 62 , 66 , 165 , 166 Second, mAbs specifically target F protein, with no effect on G, whose role in vivo has been increasingly stressed in more recent studies. 62 , 66 , 166 Moreover, also the protective potential of mAbs like Nirsevimab in the prevention of the development from RSV infection of asthma and chronic wheeze would need to be monitored over multi-year studies.…”

“… 62 , 66 , 165 , 166 Second, mAbs specifically target F protein, with no effect on G, whose role in vivo has been increasingly stressed in more recent studies. 62 , 66 , 166 Moreover, also the protective potential of mAbs like Nirsevimab in the prevention of the development from RSV infection of asthma and chronic wheeze would need to be monitored over multi-year studies. 157 , 165 …”

The Respiratory Syncytial Virus G Protein Enhances the Immune Responses to the RSV F Protein in an Enveloped Virus-like Particle Vaccine Candidate

“…Thus, most of the vaccine candidates in preclinical and clinical development are focused on inducing immune responses to the RSV F protein and many contain only the F protein (8). This focus on F protein is also due to reports of the association of G protein with enhanced respiratory disease upon RSV challenge (reviewed in Anderson, et al (10)). However, the major receptor for virus entry into human lung cells is thought to be CX3CR1, which binds the G protein (11)(12)(13)(14) .…”