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

Satabdee Mohapatra1, Guru Krishna Kumar Viswanathan1, Lukas Wettstein2

  • 1Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University Tel Aviv 69978 Israel dsegal@post.tau.ac.il.

RSC Chemical Biology
|October 27, 2021
PubMed

Insights

Ascorbic acid (vitamin C) in semen has a dual effect on semen-derived enhancer of viral infection (SEVI) amyloid formation. Low concentrations promote SEVI aggregation and HIV-1 enhancement, while high concentrations inhibit it.

Area of Science:

  • Biophysics
  • Molecular Biology
  • Virology

Background:

  • Human semen contains amyloidogenic peptides, such as PAP(248-286), that form SEVI fibrils.
  • SEVI fibrils significantly enhance HIV-1 infectivity, contributing to sexual transmission.
  • Ascorbic acid (vitamin C) is abundant in semen and known to affect amyloid aggregation.

Purpose of the Study:

  • To investigate the effect of ascorbic acid (AA) on the aggregation of PAP(248-286) in vitro.
  • To understand how AA influences the formation of SEVI fibrils and their impact on HIV-1 infectivity.

Main Methods:

  • Thioflavin T (ThT) binding assays to monitor fibril formation.
  • Transmission electron microscopy (TEM) to visualize fibril structure.
  • Circular dichroism (CD) spectroscopy to analyze secondary structure changes.
  • Cell culture assays to assess HIV-1 infectivity.

Main Results:

  • Ascorbic acid exhibited a concentration-dependent dual effect on PAP(248-286) aggregation.
  • Low AA:PAP(248-286) molar ratios promoted fibril formation.
  • High AA:PAP(248-286) molar ratios inhibited fibril formation.
  • Low AA enhanced SEVI's ability to increase HIV-1 infectivity, while high AA reduced this effect.

Conclusions:

  • Ascorbic acid modulates SEVI fibrillation in a concentration-dependent manner.
  • The findings provide biophysical insights into how a seminal component affects amyloid formation and HIV-1 infectivity.
  • Understanding this interaction may inform strategies to mitigate sexual HIV-1 transmission.