Issue 5, 2021

Dual concentration-dependent effect of ascorbic acid on PAP(248–286) amyloid formation and SEVI-mediated HIV infection

Abstract

Human semen contains various amyloidogenic peptides derived from Prostatic Acid Phosphatase (PAP) and Semenogelin proteins that are capable of enhancing HIV-1 infection when assembled into fibrils. The best characterized among them is a 39 amino acid peptide PAP(248–286), which forms amyloid fibrils termed SEVI (semen-derived enhancer of viral infection) that increase the infectivity of HIV-1 by orders of magnitude. Inhibiting amyloid formation by PAP(248–286) may mitigate the sexual transmission of HIV-1. Several vitamins have been shown to reduce the aggregation of amyloids such as Aβ, α-Synuclein, and Tau, which are associated with neurodegenerative diseases. Since ascorbic acid (AA, vitamin C) is the most abundant vitamin in semen with average concentrations of 0.4 mM, we here examined how AA affects PAP(248–286) aggregation in vitro. Using ThT binding assays, transmission electron microscopy, and circular dichroism spectroscopy, a dual and concentration-dependent behavior of AA in modulating PAP(248–286) fibril formation was observed. We found that low molar ratios of AA:PAP(248–286) promoted whereas high molar ratios inhibited PAP(248–286) fibril formation. Accordingly, PAP(248–286) aggregated in the presence of low amounts of AA enhanced HIV-1 infection, whereas excess amounts of AA during aggregation reduced the infectivity enhancing effect in cell culture. Collectively, this work provides a biophysical insight into the effect of AA, an important seminal component, on SEVI fibrillation which might impact amyloid formation kinetics, thereby modulating the biological activity of semen amyloids.

Graphical abstract: Dual concentration-dependent effect of ascorbic acid on PAP(248–286) amyloid formation and SEVI-mediated HIV infection

Supplementary files

Article information

Article type
Paper
Submitted
17 4 2021
Accepted
08 8 2021
First published
10 8 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 1534-1545

Dual concentration-dependent effect of ascorbic acid on PAP(248–286) amyloid formation and SEVI-mediated HIV infection

S. Mohapatra, G. K. K. Viswanathan, L. Wettstein, E. Arad, A. Paul, V. Kumar, R. Jelinek, J. Münch and D. Segal, RSC Chem. Biol., 2021, 2, 1534 DOI: 10.1039/D1CB00084E

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements