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Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection

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 importan...

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Autores principales: Olsen, Joanna S., Brown, Caitlin, Capule, Christina C., Rubinshtein, Mark, Doran, Todd M., Srivastava, Rajesh K., Feng, Changyong, Nilsson, Bradley L., Yang, Jerry, Dewhurst, Stephen
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975173/
https://www.ncbi.nlm.nih.gov/pubmed/20833717
http://dx.doi.org/10.1074/jbc.M110.163659
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author Olsen, Joanna S.
Brown, Caitlin
Capule, Christina C.
Rubinshtein, Mark
Doran, Todd M.
Srivastava, Rajesh K.
Feng, Changyong
Nilsson, Bradley L.
Yang, Jerry
Dewhurst, Stephen
author_facet Olsen, Joanna S.
Brown, Caitlin
Capule, Christina C.
Rubinshtein, Mark
Doran, Todd M.
Srivastava, Rajesh K.
Feng, Changyong
Nilsson, Bradley L.
Yang, Jerry
Dewhurst, Stephen
author_sort Olsen, Joanna S.
collection PubMed
description 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-EG(6) (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.
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spelling pubmed-29751732011-01-04 Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection Olsen, Joanna S. Brown, Caitlin Capule, Christina C. Rubinshtein, Mark Doran, Todd M. Srivastava, Rajesh K. Feng, Changyong Nilsson, Bradley L. Yang, Jerry Dewhurst, Stephen J Biol Chem Microbiology 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-EG(6) (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. American Society for Biochemistry and Molecular Biology 2010-11-12 2010-09-10 /pmc/articles/PMC2975173/ /pubmed/20833717 http://dx.doi.org/10.1074/jbc.M110.163659 Text en © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Microbiology
Olsen, Joanna S.
Brown, Caitlin
Capule, Christina C.
Rubinshtein, Mark
Doran, Todd M.
Srivastava, Rajesh K.
Feng, Changyong
Nilsson, Bradley L.
Yang, Jerry
Dewhurst, Stephen
Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
title Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
title_full Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
title_fullStr Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
title_full_unstemmed Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
title_short Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
title_sort amyloid-binding small molecules efficiently block sevi (semen-derived enhancer of virus infection)- and semen-mediated enhancement of hiv-1 infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975173/
https://www.ncbi.nlm.nih.gov/pubmed/20833717
http://dx.doi.org/10.1074/jbc.M110.163659
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