Inhibition of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro by carbohydrate-binding agents
Balestrieri, Emanuela × Ascolani, Arianna Igarashi, Yasuhiro Oki, Toshikazu Mastino, Antonio Balzarini, Jan Macchi, Beatrice #
American Society for Microbiology (ASM)
Antimicrobial Agents and Chemotherapy vol:52 issue:8 pages:2771-2779
Peripheral blood mononuclear cells (PBMCs) from healthy individuals can be infected by HTLV-1 upon co-cultivation of the PBMCs with irradiated HTLV-1-transformed human MT-2 cells. This model system closely mimics HTLV-1 transmission through cell-to-cell contact. Carbohydrate-binding agents (CBAs) such as the alpha(1,3)/alpha(1,6)mannose-specific Hippeastrum hybrid agglutinin (HHA) and the GlcNAc-specific Urtica dioica agglutinin (UDA), but also the small-size, nonpeptidic alpha(1,2)-mannose-specific antibiotic Pradimicin A (PRM-A) were able to efficiently prevent cell-to-cell HTLV-1 transmission at non-toxic concentrations as evidenced by the lack of appearance of virus-specific mRNA and of the viral protein Tax in the acceptor cells. Consistently, antivirally active doses of CBAs fully prevented HTLV-1-induced stimulation of PBMC growth. The inhibitory effect of CBAs on HTLV-1 transmission was evident also when HTLV-1-infected C5MJ cells were used in place of MT-2 as a virus-donor cell line. The anti-HTLV-1 properties of the CBAs highlight the importance of the envelope glycans in events underlying HTLV-1 passage from cell to cell and indicate that CBAs should be further investigated on their potential to prevent HTLV-1 infection, including mother-to-child virus transmission by cell-to-cell contact through breast milk feeding.