Prostatic acid phosphatase fragment PAPf39 (PAPf39) (PAPf39)

Prostatic acid phosphatase fragment PAPf39 is a 39-amino acid peptide (residues 248–286) derived from the proteolytic cleavage of prostatic acid phosphatase (PAP), an enzyme highly abundant in human semen (Münch et al., 2007, Nature). This fragment is notable for its ability to spontaneously self-assemble into amyloid fibrils, collectively termed Semen-derived Enhancer of Virus Infection (SEVI) (Roan et al., 2009, J. Clin. Invest.). These fibrils carry a high positive charge, which enables them to bridge the electrostatic repulsion between the negatively charged membranes of HIV-1 virions and target host cells, thereby enhancing viral infectivity by several orders of magnitude (Münch et al., 2007, Nature). Consequently, PAPf39 and the resulting SEVI fibrils are considered critical targets for the development of topical microbicides designed to block the sexual transmission of HIV (Hauber et al., 2009, PNAS). Therapeutic strategies involve using small molecules, such as epigallocatechin gallate (EGCG), or molecular tweezers like CLR01 to inhibit the aggregation of PAPf39 or to disrupt the structure and charge of existing fibrils (Lump et al., 2015, eLife). By neutralizing the proviral activity of these fibrils, these agents aim to reduce the efficiency of HIV transmission during sexual contact.

Other names

SEVISemen-derived enhancer of virus infectionPAP(248-286)Prostatic acid phosphatase 248-286

Inhibition of PAPf39 peptide aggregation into amyloid fibrils and the neutralization of the cationic surface charge of existing SEVI fibrils to prevent HIV-1 virion attachment to host cells (Hauber et al., 2009, PNAS; Lump et al., 2015, eLife).