Parainfluenza virus type 3 fusion protein (HPIV3 F protein)

The Parainfluenza virus type 3 fusion protein (HPIV3 F protein) is a class I viral fusion protein and a trimeric envelope glycoprotein present on the surface of human parainfluenza virus type 3. It mediates the fusion of the viral envelope with the host cell membrane, enabling entry of viral genetic material and subsequent infection. The F protein is synthesized as an inactive precursor (F0) that is cleaved by host cell proteases (including extracellular serine proteases like TMPRSS2) into two disulfide-linked subunits, F1 and F2, which then undergo a dramatic conformational transition during fusion. This process is triggered by receptor binding of the hemagglutinin-neuraminidase (HN) protein to host sialic acid-containing receptors, which then activates F, exposing its fusion peptide and allowing it to insert into the target cell membrane. Experimental peptide and lipopeptide fusion inhibitors can block these conformational changes by binding to the heptad repeat domains of F, thereby inhibiting viral entry. The F protein is highly conserved and a major antigenic determinant for the immune response, but antigenic variation may contribute to immune evasion and reinfection. The HPIV3 F protein is a recognized therapeutic target for antiviral drug and vaccine development, although there are currently no licensed drugs that directly target this protein in clinical use.

Other names

Human parainfluenza virus type 3 fusion proteinHPIV3 FFusion glycoprotein (F)Parainfluenza virus 3 F protein

Inhibition of conformational changes required for membrane fusion by binding to heptad repeat regions, thus preventing six-helix bundle formation and blocking viral entry