Respiratory syncytial virus fusion glycoprotein, antigenic site II (RSV F site II)

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a type I integral membrane protein essential for viral entry, mediating the fusion of the viral envelope with the host cell membrane [Frontiers in Immunology, 2024; PMC NIH, 2013]. Antigenic site II is a prominent, highly conserved epitope on the F protein that is present in both its metastable prefusion and stable postfusion conformations [Frontiers in Immunology, 2024; PMC NIH, 2015]. This site is the target of palivizumab, the first monoclonal antibody approved for the prevention of severe RSV disease in high-risk infants [Frontiers in Immunology, 2024; ASM Journals, 2010]. Antibodies binding to site II neutralize the virus by blocking the structural transitions of the F protein required for fusion, thereby preventing the delivery of the viral genome into the host cell [ASM Journals, 2010; PMC NIH, 2015]. Although newer therapies targeting prefusion-specific epitopes like site Ø have emerged, site II remains a critical target for immunoprophylaxis and vaccine design [Frontiers in Immunology, 2024; MDPI, 2024]. Resistance to site II-directed antibodies can occur through specific amino acid substitutions within the epitope, such as at positions 262, 272, and 275 [ASM Journals, 2010; MDPI, 2024]. The site is characterized by a helix-loop-helix motif and is recognized by several neutralizing antibodies that inhibit both virus-to-cell and cell-to-cell fusion [ASM Journals, 2010; PMC NIH, 2022]. Clinical use of site II-targeted agents has significantly reduced hospitalizations in vulnerable pediatric populations [Frontiers in Immunology, 2024; AIR Unimi, 2025].

Other names

Site II [Frontiers in Immunology, 2024]Site A [ASM Journals, 2010]Palivizumab epitope [PMC NIH, 2015]Motavizumab epitope [PLOS One, 2019]Respiratory syncytial virus fusion protein site II [PMC NIH, 2013]

Neutralization of viral infectivity by inhibiting membrane fusion between the viral envelope and the host cell membrane [Frontiers in Immunology, 2024; ASM Journals, 2010; PMC NIH, 2015].