Blocking Semen-Mediated Enhancement of HIV Infection by Amyloid-Binding Small Molecules

Abstract

Evaluation of: Olsen JS, Brown C, Capule CC et al.: Amyloid-binding small molecules efficiently block SEVI (semen-derived enhancer of virus infection)- and semen-mediated enhancement of HIV-1 infection. J. Biol. Chem. 285(46), 35488–35496 (2010). Sexual intercourse is the major route for the spread of the AIDS pandemic and semen represents the main vector for HIV-1 transmission. It is under debate whether semen enhances or inhibits HIV-1 infection. However, accumulating evidence suggests that semen contains amyloid aggregates (termed ‘semen-derived enhancer of virus infection’ [SEVI]) that boost infection and thus represent a promising target for the prevention of HIV-1 transmission. Here, Olsen and colleagues demonstrate that BTA-EG6, a derivative of the amyloid-specific dye thioflavin T, binds SEVI fibrils. This interaction blocks the ability of SEVI to enhance virus infection by preventing the association of SEVI with target cells. Importantly, the authors also demonstrate that BTA-EG6 inhibits semen-mediated enhancement of HIV-1 infection without causing inflammation or toxicity in cervical cells. These results suggest that small amyloid-binding molecules that block semen-mediated enhancement of HIV-1 infection are a useful supplement to microbicides for preventing sexual transmission of the virus.