Abstract
Amyloid fibrils contained in semen, known as SEVI, or semen-derived enhancer of viral infection, have been shown to increase the infectivity of HIV dramatically. However, previous work with these fibrils has suggested that extensive time and nonphysiologic levels of agitation are necessary to induce amyloid formation from the precursor peptide (a proteolytic cleavage product of prostatic acid phosphatase, PAP(248-286)). Here, we show that fibril formation by PAP(248-286) is accelerated dramatically in the presence of seminal plasma (SP) and that agitation is not required for fibrillization in this setting. Analysis of the effects of specific SP components on fibril formation by PAP(248-286) revealed that this effect is primarily due to the anionic buffer components of SP (notably inorganic phosphate and sodium bicarbonate). Divalent cations present in SP had little effect on the kinetics of fibril formation, but physiologic levels of Zn(2+) strongly protected SEVI fibrils from degradation by seminal proteases. Taken together, these data suggest that in the in vivo environment, PAP(248-286) is likely to form fibrils efficiently, thus providing an explanation for the presence of SEVI in human semen.
Highlights
SEVI is an amyloid fibril that enhances HIV infectivity
The use of this semen simulant (referred to hereafter as “artificial semen” (AS)) allowed us to dissect the requirements for seminal plasma (SP)-enhanced fibril formation while eliminating the possibility that preexisting SEVI fibrils or oligomers might contribute to the accelerated kinetics of fibril formation
Previous studies have noted that semen may contain substances that both enhance (5–7, 22, 23) and inhibit HIV-1 infection (24 –26)
Summary
SEVI is an amyloid fibril that enhances HIV infectivity To date, it has been produced from its precursor peptide only under nonphysiologic conditions. Previous work with these fibrils has suggested that extensive time and nonphysiologic levels of agitation are necessary to induce amyloid formation from the precursor peptide (a proteolytic cleavage product of prostatic acid phosphatase, PAP248–286). Divalent cations present in SP had little effect on the kinetics of fibril formation, but physiologic levels of Zn2؉ strongly protected SEVI fibrils from degradation by seminal proteases. Taken together, these data suggest that in the in vivo environment, PAP248–286 is likely to form fibrils efficiently, providing an explanation for the presence of SEVI in human semen
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
