Respiratory syncytial virus fusion protein (RSV F) (prefusion conformation, epitope VI) (RSV pre-F epitope VI)

The Respiratory syncytial virus (RSV) fusion (F) protein is a class I viral fusion protein essential for viral entry and the formation of syncytia (McLellan et al., 2013, Science). It is the primary target for neutralizing antibodies and vaccine development, existing in a metastable prefusion conformation (pre-F) and a stable postfusion conformation (post-F) (NIH, 2023). Epitope VI, also known as Antigenic Site VI, is a recently characterized, prefusion-specific epitope located on the membrane-proximal stalk of the F1 subunit, near the viral membrane (Zhang et al., 2021, Nature Communications). This site is distinct from the immunodominant apical sites, such as Site Ø and Site V, and appears to be more conserved across RSV subtypes A and B (Guo et al., 2023, ASM). Antibodies targeting Epitope VI, such as the experimental single-domain antibodies m17 and m35, neutralize the virus by preventing the structural transition from the prefusion to the postfusion state, thereby inhibiting membrane fusion (Zhang et al., 2021). RSV is a major cause of severe lower respiratory tract infections, including bronchiolitis and pneumonia, in infants, the elderly, and immunocompromised individuals (NIH, 2023). Targeting Epitope VI offers a strategic advantage for developing broad-spectrum prophylactics that may bypass the immune pressure and antigenic drift associated with apical epitopes.

Other names

Antigenic site VISite VIRSV F site VIRSV F epitope VIPrefusion-specific epitope VI

Neutralization of the virus by stabilizing the prefusion conformation of the F protein and preventing the conformational rearrangement required for membrane fusion.