Soluble Globotriaosylceramide as a Potential Systemic and Local Inhibitor of HIV Infection

• Main Author: Harrison, Amanda L.
• Other Authors: Branch, Donald R.
• Language: en_ca
• Published: 2009
• Subjects: Pathology 0571
• Online Access: http://hdl.handle.net/1807/17511

Previously we have identified the glycosphingolipid globotriaosylceramide (Gb3/Pk) as an inhibitor and resistance factor against HIV-1 infection in vitro. Here we show that a novel, soluble, completely synthetic Gb3 analogue, FSLGb3, inhibits infection of X4 strains of HIV-1 in the Jurkat T-cell line and both R5 and X4 strains in PBMCs. FSLGb3 absorbs into cellular plasma membranes and membrane adsorbed FSLGb3 was able to inhibit subsequent HIV-1 infection. We have also developed a mouse model to test in vivo the efficacy of soluble Gb3 analogs in the prevention of mucosal viral infection. Soluble Gb3 was incorporated into gel or alone and applied directly to the vaginal and rectal mucosal tissue of mice. We have not yet shown a statistically significant reduction in infection, although a trend towards inhibition is evident. Our studies show synthetic Gb3 to be an inhibitor of HIV-1 infection and further exploration of therapeutic strategies are warranted.