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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.

Original publication

DOI

10.1128/AAC.01550-07

Type

Journal article

Journal

Antimicrob Agents Chemother

Publication Date

02/2009

Volume

53

Pages

678 - 687

Keywords

Antiviral Agents, Cell Fusion, Cell Survival, Cells, Cultured, Gene Products, env, HTLV-I Infections, HeLa Cells, Human T-lymphotropic virus 1, Humans, Naphthalenesulfonates, Peptides, Polymers, Retroviridae Proteins, Oncogenic, Reverse Transcriptase Polymerase Chain Reaction, Virion