Amyloid-binding small molecules efficiently block SEVI (Semen-derived Enhancer of Virus Infection)- and semen-mediated enhancement of HIV-1 infection

Joanna S. Olsen, Caitlin Brown, Christina C. Capule, Mark Rubinshtein, Todd M. Doran, Rajesh K. Srivastava, Changyong Feng, Bradley L. Nilsson, Jerry Yang, Stephen Dewhurst

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Semen was recently shown to contain amyloid fibrils formed from a self-assembling peptide fragment of the protein prostatic acid phosphatase. These amyloid fibrils, termed semen-derived enhancer of virus infection, or SEVI, have been shown to strongly enhance HIV infectivity and may play an important role in sexual transmission of HIV, making them a potential microbicide target. One novel approach to target these fibrils is the use of small molecules known to intercalate into the structure of amyloid fibrils, such as derivatives of thioflavin-T. Here, we show that the amyloid-binding small molecule BTA-EG6 (the hexa(ethylene glycol) derivative of benzothiazole aniline) is able to bind SEVI fibrils and effectively inhibit both SEVI-mediated and semen-mediated enhancement of HIV infection. BTA-EG 6 also blocks the interactions of SEVI with HIV-1 virions and HIV-1 target cells but does not cause any inflammation or toxicity to cervical epithelial cells. These results suggest that an amyloid-binding small molecule may have utility as a microbicide, or microbicidal supplement, for HIV-1.

Original languageEnglish (US)
Pages (from-to)35488-35496
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number46
DOIs
StatePublished - Nov 12 2010

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