Seminal Plasma Accelerates Semen-derived Enhancer of Viral Infection (SEVI) Fibril Formation by the Prostatic Acid Phosphatase (PAP248–286) Peptide

• Published in: The Journal of biological chemistry 2012-04, Vol.287 (15), p.11842-11849
• Main Authors: Olsen, Joanna S., DiMaio, John T.M., Doran, Todd M., Brown, Caitlin, Nilsson, Bradley L., Dewhurst, Stephen
• Format: Article
• Language: English
• Subjects: Acid phosphatase; Agitation; Amyloid; Amyloid - chemistry; Amyloid - metabolism; Amyloid - ultrastructure; Animal Viruses; Buffers; Cell Line; Data processing; Fibrillogenesis; Fibrils; HIV Infections - virology; HIV-1; HIV-1 - pathogenicity; Human Immunodeficiency Virus; Humans; Infection; Infectivity; Kinetics; Microbiology; Peptide Fragments - chemistry; Peptide Fragments - physiology; Peptide Hydrolases - chemistry; Phosphate; Protein Multimerization; Protein Stability; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - physiology; Proteinase; Proteolysis; Semen; Semen - chemistry; Semen - metabolism; Seminal Plasma; SEVI; Sodium bicarbonate; Substance P; Virus Entry; Zinc; Zinc - chemistry
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.314336

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, PAP248–286). Here, we show that fibril formation by PAP248–286 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 PAP248–286 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 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, thus providing an explanation for the presence of SEVI in human semen. Background: SEVI is an amyloid fibril that enhances HIV infectivity. To date, it has been produced from its precursor peptide only under nonphysiologic conditions. Results: Seminal plasma (SP) accelerates SEVI formation and protects SEVI from proteolytic degradation. Conclusion: SEVI forms spontaneously from its precursor peptide under physiologic conditions in SP. Significance: These findings may explain the presence of SEVI in human semen.