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

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.

Targeting Trojan Horse leukocytes for HIV prevention

“…Antibodies and peptides that block LFA/ICAM and MAC-1/JAM C interactions and sulfated polysaccharides inhibit attachment of leukocytes to epithelial cells and, therefore, could inhibit cell-associated HIV transmission [285–287]. ICAMs are also important components of viral synapses; therefore, ICAM blockers could also block this cell-associated HIV transmission mechanism.…”

Sexual transmission of human T-cell lymphotropic virus type 1

“…Studies on candidate topical microbicides suggest that these agents might reduce HTLV-1 sexual transmission 93 and reduce circulating proviral loads without affecting host immune systems; topical microbicides are potential therapeutic agents for the prevention and treatment of HTLV-1-associated diseases 95 .…”

“…Additionally, HTLV-1 antiserum, which contains high titers of anti-Env neutralizing antibodies, was a potent inhibitor in most of the assays, indicating that neutralizing antibodies in patient sera might play an important role in protection against HTLV-1 transmission, particularly if the antibodies are also at high titers in vaginal secretions. The presence of these antibodies might help limit HTLV-1 transmission via cervicovaginal secretions 93 .…”

A Nationwide Antenatal Human T-Cell Leukemia Virus Type-1 Antibody Screening in Japan

“…In animal experiments, it was reported that the administration of HTLV-1 antibody (Kuo et al, 2011;Fujii et al, 2016;Murakami et al, 2017) and the use of polyanionic microbicides are effective in preventing MTCT (Romer et al, 2009), but they are not ready for human use yet.…”