Respiratory syncytial virus fusion glycoprotein (subtype B) (RSV F (subtype B))

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a class I viral fusion protein essential for the entry of the virus into host cells [2, 7]. It is synthesized as an inactive precursor, F0, which is cleaved into F1 and F2 subunits that form a metastable prefusion trimer [8, 10]. Upon contact with the host cell membrane, the prefusion F protein undergoes a dramatic and irreversible conformational change into a stable postfusion state, a process that drives the fusion of viral and cellular membranes [17, 19]. Subtype B is one of the two major antigenic groups of RSV, and while its F protein shares high sequence identity with subtype A, it possesses distinct amino acid variations in key neutralizing epitopes [1, 4]. The prefusion conformation is the primary target for modern vaccines and monoclonal antibodies because it displays highly potent neutralizing sites, such as site Ø and site V, which are absent in the postfusion form [1, 8]. Therapeutic agents like nirsevimab and bivalent vaccines such as Abrysvo are designed to stabilize or target this prefusion state to block viral infection and prevent severe lower respiratory tract diseases like bronchiolitis and pneumonia [1, 5, 6]. Monitoring neutralizing antibody titers against the prefusion F protein serves as a key biomarker for vaccine efficacy and protection [18, 21].

Other names

RSV F proteinFusion glycoprotein F0RSV PreFRSV F1/F2Respiratory syncytial virus B fusion proteinRSV-B F protein

Drugs and vaccines targeting the prefusion F glycoprotein work by binding to and stabilizing the protein in its metastable prefusion conformation [13, 14]. This prevents the irreversible structural rearrangement into the postfusion state, which is necessary for the fusion of the viral envelope with the host cell membrane, thereby blocking viral entry and infection [17, 19].