Inhibition of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro by carbohydrate-binding agents

Antimicrob Agents Chemother. 2008 Aug;52(8):2771-9. doi: 10.1128/AAC.01671-07. Epub 2008 May 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutinins / pharmacology*
  • Anthracyclines / pharmacology
  • Antiviral Agents / pharmacology*
  • Blotting, Western
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism
  • Human T-lymphotropic virus 1 / drug effects*
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / metabolism
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / virology
  • Liliaceae / chemistry
  • Mannose / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urtica dioica / chemistry

Substances

  • Agglutinins
  • Anthracyclines
  • Antiviral Agents
  • Gene Products, tax
  • pradimicin A
  • Mannose