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Antimicrobial Agents and Chemotherapy, February 2009, p. 678-687, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.01550-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Candidate Polyanionic Microbicides Inhibit Human T-Cell Lymphotropic Virus Type 1 Receptor Interactions, Cell-Free Infection, and Cell-Cell Spread{triangledown}

Daniela Romer,1* David W. Brighty,2 Cynthia L. Robson,1 and Quentin J. Sattentau1

The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom,1 Biomedical Research Centre, University of Dundee, Dundee DD1 9SY, United Kingdom2

Received 2 December 2007/ Returned for modification 7 February 2008/ Accepted 5 September 2008

The human T-cell lymphotropic virus type 1 (HTLV-1) is the cause of adult T-cell leukemia and inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 can be transmitted through sexual contact, mother-to-child transmission, and exposure to contaminated blood. Microbicides are agents that interfere with microbial infectivity at mucous membranes, and candidates are under development for use against sexually transmitted viruses such as human immunodeficiency virus type 1. We previously demonstrated that cell surface polyanionic heparan sulfate proteoglycans bind the HTLV-1 envelope glycoprotein surface subunit gp46, facilitating cell-cell and cell-free virus spread in vitro. We now show, using assays for Env-receptor binding inhibition, Env-induced cell-cell fusion, cell-cell virus spread, and pseudotype HTLV-1 infectivity, that the soluble polyanions PRO 2000 and dextran sulfate are potent inhibitors of HTLV-1 spread in vitro, with PRO 2000 being the more promising candidate. The results of these studies suggest that candidate topical microbicides may be of use in reducing HTLV-1 sexual transmission.

* Corresponding author. Mailing address: The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom. Phone: 44 1865 275510. Fax: 44 1865 275511. E-mail: roemer.daniela{at}web.de

{triangledown} Published ahead of print on 1 December 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 678-687, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.01550-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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