Respiratory syncytial virus fusion glycoprotein (prefusion conformation, subgroup A) (RSV F (pre-F))

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a class I viral fusion protein that is essential for the virus to enter host cells by mediating the fusion of the viral envelope with the host cell membrane (McLellan et al., Science, 2013). It is synthesized as an inactive precursor that is cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion trimer (pre-F). Upon contact with the host cell, the pre-F protein undergoes a dramatic and irreversible conformational change into a stable postfusion (post-F) state to drive membrane merging (Graham, Science, 2017). The prefusion conformation is the primary target for potent neutralizing antibodies because it displays unique, highly sensitive antigenic sites, such as Site Ø and Site V, which are lost during the transition to the postfusion form (Jones et al., Nature Communications, 2019). Subgroup A refers to one of the two major antigenic lineages of RSV, and the F protein from this subgroup is a key component in modern stabilized subunit vaccines and monoclonal antibodies. Therapeutic strategies targeting the pre-F protein, such as nirsevimab and the vaccines Arexvy and Abrysvo, aim to prevent severe lower respiratory tract disease, including bronchiolitis and pneumonia, in high-risk populations like infants and older adults (FDA, Arexvy Prescribing Information, 2023). By binding to the pre-F state, these agents block the structural rearrangement necessary for infection, effectively neutralizing the virus (Hammitt et al., NEJM, 2022).

Other names

RSV F proteinRSV-FFusion glycoproteinPrefusion FRSV A F proteinRSV fusion protein subgroup A

Neutralization of viral entry by binding to the prefusion conformation of the F protein, thereby preventing the conformational change to the postfusion state required for membrane fusion (McLellan et al., Science, 2013).