Polyanionic Candidate Microbicides Accelerate the Formation of Semen-Derived Amyloid Fibrils to Enhance HIV-1 Infection
Figure 10
Schematic presentation of drug-protein interaction that result in the poor efficacy of polyanionic candidate microbicides in clinical trials.
Prior to the sexual intercourse, candidate microbicide was intravaginally applied and these anionic macromolecules remained on the vaginal surface rather than distributed in the inner tissue. When the viruses arrived, polyanions neutralized the viruses and stopped HIV at the gate (I). However, during sexual intercourse, viruses were delivered in semen, in which cationic peptides/proteins competitively interacted with polyanions so that there might not be sufficient polyanions to interfere with HIV-1 infection (II). Even worse, the interaction between polyanions and PAP derived fragments led to a facilitated process of amyloid fibril formation. The accelerated amyloid fibril formation increased the risk of HIV sexual transmission (III). Green particles, polyanionic molecules, purple particles, PAP derived fragments, orange particles, non-PAP derived cationic peptides/proteins.