Respiratory syncytial virus Fusion glycoprotein (RSV F) (RSV F)

The Respiratory syncytial virus (RSV) Fusion (F) glycoprotein is a critical class I viral fusion protein that mediates the fusion of the viral envelope with the host cell membrane, a process essential for viral entry and the formation of multinucleated syncytia. It is synthesized as an inactive precursor (F0) that is cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion trimer (preF). Upon triggering, the protein undergoes a dramatic conformational rearrangement into a highly stable postfusion state (postF). Antigenic site III is a highly conserved epitope located on the midsection of the F protein head, involving residues from domains I, II, and III. While site III is present in both preF and postF conformations, antibodies targeting this site often exhibit a preference for the prefusion form and can provide broad neutralization across different RSV strains and even related viruses like human metapneumovirus (hMPV). Therapeutic strategies targeting site III, such as the monoclonal antibody MPE8, aim to block the fusion process, thereby preventing infection and reducing the severity of RSV-associated diseases like bronchiolitis and pneumonia. This site is particularly valuable for the development of cross-reactive therapeutics due to its high degree of sequence conservation among pneumoviruses. However, the emergence of viral escape mutants remains a significant challenge for monoclonal antibodies targeting this specific epitope. Monitoring of circulating strains is necessary to ensure continued efficacy of site III-directed therapies. Overall, site III represents a key target for both passive immunization and structure-based vaccine design.

Other names

RSV F proteinFusion proteinAntigenic site IIISite IIIRespiratory syncytial virus F glycoprotein

Neutralization of viral entry by binding to the F protein and inhibiting the conformational change required for membrane fusion.