Parainfluenza virus type 3 prefusion fusion protein (PIV3 prefusion F protein)

The Parainfluenza virus type 3 prefusion fusion protein is a trimeric, surface-expressed viral glycoprotein crucial for HPIV3 entry into host cells. In its native, metastable prefusion state, the F protein is activated by the hemagglutinin-neuraminidase (HN) protein upon receptor engagement. Proteolytic cleavage releases the fusion peptide, triggering dramatic conformational changes that facilitate the merger of the viral envelope with the host membrane, allowing viral genome entry. The prefusion conformation exposes key antigenic sites targeted by strongly neutralizing antibodies, making this form of the F protein a leading antigen for vaccine development and antibody-based prophylaxis or therapy. Stabilized prefusion F proteins elicit substantially higher levels of neutralizing antibodies than postfusion conformers and are the basis for ongoing HPIV3 vaccine efforts. No licensed HPIV3 vaccines or F-directed antivirals currently exist, but preclinical/clinical candidates are in development[1][10][7][13].

Other names

Fusion glycoprotein F (prefusion form)HPIV3 F protein (prefusion)Human parainfluenza virus 3 F protein (prefusion)

Neutralizing antibodies or vaccine-elicited antibodies block transition from prefusion to postfusion state, preventing membrane fusion and viral entry[1][10][7] Antibodies targeting the prefusion conformation are much more potently neutralizing than those targeting the postfusion state[10][1] Some small molecules may inactivate the virus by prematurely triggering conformational changes in F, rendering the virus non-infectious[6]