Human metapneumovirus fusion glycoprotein (prefusion conformation) (hMPV F)

The human metapneumovirus (hMPV) fusion (F) glycoprotein is a critical Class I viral fusion protein that facilitates the entry of the virus into host respiratory epithelial cells by mediating membrane fusion (Battles et al., 2017, Nature Communications). It is synthesized as an inactive precursor (F0) that is cleaved into disulfide-linked F1 and F2 subunits, which then assemble into a metastable prefusion trimer (UniProt P0C2Z1). This prefusion conformation is the primary target for the host's neutralizing antibody response, as it contains highly conserved and potent epitopes that are lost when the protein triggers and rearranges into its stable post-fusion state (PubMed: 28413138). hMPV is a leading cause of pediatric bronchiolitis and pneumonia, as well as severe respiratory disease in the elderly and immunocompromised (NIH: StatPearls). Therapeutic strategies focus on stabilizing the prefusion conformation using proline substitutions or disulfide bonds to create effective vaccine antigens, such as those used in mRNA-1653, or to develop monoclonal antibodies like DS7 that block the fusion process (Moderna; PubMed: 31511395). By maintaining the protein in its prefusion state, these interventions prevent the structural collapse into the post-fusion form that is necessary for the viral and host membranes to merge. Consequently, the prefusion F protein is considered a superior immunogen compared to the post-fusion form for the development of next-generation vaccines and therapeutics (PubMed: 28413138).

Other names

hMPV F proteinHuman metapneumovirus F glycoproteinPrefusion F proteinhMPV fusion protein

Stabilization of the prefusion conformation to prevent the irreversible transition to the post-fusion state, thereby inhibiting viral-host membrane fusion and neutralizing infectivity.