Respiratory syncytial virus fusion glycoprotein, prefusion trimer (RSV PreF)

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein, specifically in its prefusion trimer conformation, is a critical class I viral fusion protein located on the surface of the RSV virion. It is essential for the virus's ability to infect host cells by mediating the fusion of the viral envelope with the host cell plasma membrane (1, 3, 17). The protein is synthesized as an inactive precursor (F0) that is cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion trimer (1, 4, 13). Upon triggering, the prefusion trimer undergoes a dramatic and irreversible conformational change into a highly stable postfusion form, a process that drives the fusion of membranes (4, 12, 20). As a therapeutic target, the prefusion trimer is highly valued because it contains potent neutralizing epitopes, such as antigenic site Ø and site V, which are lost during the transition to the postfusion state (5, 10, 20). Modern vaccines like Arexvy and Abrysvo, as well as long-acting monoclonal antibodies like nirsevimab, specifically target or utilize the stabilized prefusion conformation to elicit or provide high-titer neutralizing antibodies (4, 8, 11, 15). These interventions are designed to prevent severe lower respiratory tract diseases, such as bronchiolitis and pneumonia, particularly in vulnerable populations like infants and the elderly (1, 2, 22). Targeting the prefusion state has revolutionized RSV prevention, overcoming decades of challenges associated with less effective postfusion-based approaches and historical safety concerns like enhanced respiratory disease (5, 13, 15).

Other names

RSV F proteinPrefusion FPreFRSV fusion proteinRSV F glycoproteinRSV F0RSV F1/F2 subunitsRespiratory syncytial virus fusion protein

Neutralization of the virus by binding to highly conserved epitopes (e.g., site Ø) on the prefusion conformation, thereby inhibiting the conformational change required for viral-host membrane fusion and blocking viral entry into host cells.