Respiratory syncytial virus fusion protein (prefusion conformation, Site III) (RSV PreF Site III)

The Respiratory syncytial virus (RSV) fusion (F) protein is a class I viral fusion glycoprotein that is essential for the virus to enter host cells by mediating the fusion of the viral envelope with the host cell membrane [1.4.1, 1.4.2]. It is synthesized as an inactive precursor (F0) that is proteolytically cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion trimer [1.1.4, 1.4.1]. Site III is a highly conserved antigenic epitope located on the side of this trimer and is accessible in both the prefusion and postfusion conformations, though many potent neutralizing antibodies show a preference for the prefusion state [1.3.1, 1.3.5]. Antibodies targeting Site III, such as the monoclonal antibody MPE8, can cross-neutralize both RSV and human metapneumovirus (hMPV) due to the high structural conservation of this site across the Pneumoviridae family [1.2.1, 1.3.4]. By binding to Site III, these agents prevent the dramatic structural rearrangement of the F protein into its postfusion form, effectively blocking viral entry [1.1.2, 1.3.4]. This site is a critical focus for the development of next-generation vaccines and therapeutic monoclonal antibodies aimed at providing broad protection against respiratory infections [1.2.1, 1.3.1].

Other names

Antigenic site IIIRSV F Site 3Site III epitopePrefusion F protein site III

Neutralization of viral entry by binding to the F protein and preventing the conformational transition from the metastable prefusion state to the stable postfusion state, thereby inhibiting membrane fusion between the viral envelope and the host cell membrane [1.1.2, 1.3.4].