Human metapneumovirus fusion protein (hMPV F) (hMPV F)

The human metapneumovirus (hMPV) fusion (F) protein is a critical Type I viral surface glycoprotein that facilitates viral entry by mediating the fusion of the viral envelope with the host cell membrane (UniProt: P0C2Z1). It is synthesized as an inactive precursor that is proteolytically cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion (preF) trimer. This preF conformation is the primary target for neutralizing antibodies because it contains the most potent and conserved epitopes required for blocking viral entry (Battles et al., Nat Commun, 2017). Upon triggering, the preF protein undergoes a massive conformational change into a stable postfusion (postF) state, a process that drives the fusion of membranes. Therapeutic strategies, including monoclonal antibodies like MPE8 and vaccine candidates like mRNA-1653, focus on stabilizing the preF state to elicit or provide high-titer neutralizing antibodies (Wen et al., Nat Commun, 2017; Moderna, 2024). These treatments are designed to prevent severe lower respiratory tract infections, such as bronchiolitis and pneumonia, particularly in vulnerable populations like infants and the elderly. By binding to the preF protein, neutralizing antibodies can sterically block the fusion process or prevent the protein from transitioning to its active state, effectively neutralizing the virus's ability to infect cells.

Other names

hMPV F proteinHuman metapneumovirus fusion glycoproteinhMPV preFFusion protein F1/F2hMPV fusion protein

Neutralization of viral infectivity by binding to the prefusion conformation of the F protein, thereby preventing the structural transition to the postfusion state and inhibiting membrane fusion with the host cell.