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

Satabdee Mohapatra, Guru Krishna Kumar Viswanathan, Lukas Wettstein, Elad Arad, Ashim Paul, Vijay Kumar, Raz Jelinek, Jan Münch, Daniel Segal

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)1534-1545
Number of pages12
JournalRSC Chemical Biology
Volume2
Issue number5
DOIs
StatePublished - 1 Oct 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Chemistry (miscellaneous)

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