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Antimicrobial Agents and Chemotherapy, December 2001, p. 3427-3432, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3427-3432.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Papillomavirus Microbicidal Activities of High-Molecular-Weight Cellulose Sulfate, Dextran Sulfate, and Polystyrene Sulfonate

Neil D. Christensen,1,2,* Cynthia A. Reed,1 Tim D. Culp,2 Paul L. Hermonat,3 Mary K. Howett,2 Robert A. Anderson,4 and Lourens J. D. Zaneveld4

The Jake Gittlen Cancer Research Institute and Department of Pathology1 and Department of Microbiology and Immunology,2 The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Department of Obstetrics-Gynecology, University of Arkansas Medical School, Little Rock, Arkansas 722053; and Section of Obstetrics-Gynecology Research, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 606124

Received 1 June 2001/Returned for modification 7 August 2001/Accepted 10 September 2001

The high-molecular-weight sulfated or sulfonated polysaccharides or polymers cellulose sulfate, dextran sulfate, and polystyrene sulfonate were tested for microbicidal activity against bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 11 (HPV-11) and type 40 (HPV-40). In vitro assays included the BPV-1-induced focus-forming assay and transient infection of human A431 cells with HPVs. The compounds were tested for microbicidal activity directly by preincubation with virus prior to addition to cell cultures and indirectly by addition of virus to compound-treated cells and to virus-coated cells to test inactivation of the virus after virus-cell binding. The data indicated that all three compounds showed direct microbicidal activity with 50% effective concentrations between 10 to 100 µg/ml. These concentrations were nontoxic to cell cultures for both assays. When a clone of C127 cells was tested for microbicidal activity, approximately 10-fold-less compound was required to achieve a 50% reduction in BPV-1-induced foci than for the uncloned parental C127 cells. Pretreatment of cells with compound prior to addition of virus also demonstrated strong microbicidal activity with dextran sulfate and polystyrene sulfonate, but cellulose sulfate required several orders of magnitude more compound for virus inactivation. Polystyrene sulfonate prevented subsequent infection of HPV-11 after virus-cell binding, and this inactivation was observed up to 4 h after addition of virus. These data indicate that the polysulfated and polysulfonated compounds may be useful nontoxic microbicidal compounds that are active against a variety of sexually transmitted disease agents including papillomaviruses.


* Corresponding author. Mailing address: The Jake Gittlen Cancer Research Institute and Departments of Pathology and of Microbiology and Immunology, The Milton S. Hershey Medical Center, 500 University Dr., Hershey, PA 17033. Phone: (717) 531-6185. Fax: (717) 531-5634. E-mail: ndc1{at}psu.edu.


Antimicrobial Agents and Chemotherapy, December 2001, p. 3427-3432, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3427-3432.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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