Affiliation:
1. The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
2. Biomedical Research Centre, University of Dundee, Dundee DD1 9SY, United Kingdom
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference53 articles.
1. Anderson, R. A., K. A. Feathergill, X. H. Diao, M. D. Cooper, R. Kirkpatrick, B. C. Herold, G. F. Doncel, C. J. Chany, D. P. Waller, W. F. Rencher, and L. J. Zaneveld. 2002. Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent. J. Androl.23:426-438.
2. Baba, M., R. Pauwels, J. Balzarini, J. Arnout, J. Desmyter, and E. De Clercq. 1988. Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro. Proc. Natl. Acad. Sci. USA85:6132-6136.
3. Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus
4. Balzarini, J., Y. Van Herrewege, K. Vermeire, G. Vanham, and D. Schols. 2007. Carbohydrate-binding agents efficiently prevent dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1 transmission to T lymphocytes. Mol. Pharmacol.71:3-11.
5. Bartholomew, C., W. C. Saxinger, J. W. Clark, M. Gail, A. Dudgeon, B. Mahabir, B. Hull-Drysdale, F. Cleghorn, R. C. Gallo, and W. A. Blattner. 1987. Transmission of HTLV-I and HIV among homosexual men in Trinidad. JAMA257:2604-2608.
Cited by
11 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献