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

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., 2013, Science). The F protein is synthesized as an inactive precursor (F0) that is cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion trimer (pre-F). Upon contact with a host cell, the pre-F protein undergoes a massive, irreversible conformational change into a stable postfusion (post-F) state, a process that drives the merger of viral and cellular membranes (Graham, 2017, Immunological Reviews). The prefusion conformation is the primary target for modern therapeutic development because it contains highly potent neutralizing epitopes, such as Site Ø and Site V, which are lost when the protein transitions to the postfusion state (Battles & McLellan, 2019, Nature Reviews Microbiology). Subtype A is one of the two major antigenic groups of RSV; while the F protein is highly conserved between subtypes A and B, subtype-specific variations can influence the binding affinity of certain monoclonal antibodies (Jones et al., 2023, NEJM). Current clinical interventions, including the monoclonal antibody nirsevimab and stabilized prefusion F vaccines like Arexvy and Abrysvo, specifically target this conformation to prevent severe lower respiratory tract disease in infants and older adults (Simoes et al., 2022, Lancet Child & Adolescent Health).

Other names

RSV F proteinPrefusion FRSV-FFusion glycoprotein F0RSV subtype A fusion protein

Neutralization of viral infectivity by binding to the prefusion conformation of the F protein, thereby preventing the structural rearrangement required for membrane fusion and viral entry into host cells.