Inhibition of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro by carbohydrate-binding agents.
Peripheral blood mononuclear cells (PBMCs) from healthy individuals can be infected by human T-lymphotropic virus type 1 (HTLV-1) upon cocultivation 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 and the GlcNAc-specific Urtica dioica agglutinin, and also the small, nonpeptidic alpha(1,2)-mannose-specific antibiotic pradimicin A, were able to efficiently prevent cell-to-cell HTLV-1 transmission at nontoxic 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 effects of CBAs on HTLV-1 transmission were also evident when HTLV-1-infected C5MJ cells were used in place of MT-2 cells 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 for their potential to prevent HTLV-1 infection, including mother-to-child virus transmission by cell-to-cell contact through breast milk feeding.
Balestrieri
Emanuela
E
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00135 Rome, Italy.
Ascolani
Arianna
A
Igarashi
Yasuhiro
Y
Oki
Toshikazu
T
Mastino
Antonio
A
Balzarini
Jan
J
Macchi
Beatrice
B
D000373:Agglutinins / Q000494:pharmacology*; D018943:Anthracyclines / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D019668:Liliaceae / Q000737:chemistry; D008358:Mannose / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026982:Urtica dioica / Q000737:chemistry; D000095643:Pradimicins and Benanomicins
D000373:Agglutinins; D018943:Anthracyclines; D000998:Antiviral Agents; D016356:Gene Products, tax; D008358:Mannose; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins