Candidate polyanionic microbicides inhibit human T-cell lymphotropic virus type 1 receptor interactions, cell-free infection, and cell-cell spread.
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.
Romer
Daniela
D
The Sir William Dunn School of Pathology, University of Oxford, United Kingdom. roemer.daniela@web.de
Brighty
David W
DW
Robson
Cynthia L
CL
Sattentau
Quentin J
QJ
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002459:Cell Fusion; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015686:Gene Products, env / Q000187:drug effects; D015490:HTLV-I Infections / Q000517:prevention & control* / Q000635:transmission; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects*; D006801:Humans; D009282:Naphthalenesulfonates / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D015682:Retroviridae Proteins, Oncogenic / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014771:Virion / Q000187:drug effects
D000998:Antiviral Agents; D015686:Gene Products, env; D009282:Naphthalenesulfonates; C120231:PRO 2000; D010455:Peptides; D011108:Polymers; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I