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Antimicrobial Agents and Chemotherapy, August 2008, p. 2771-2779, Vol. 52, No. 8
0066-4804/08/$08.00+0     doi:10.1128/AAC.01671-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inhibition of Cell-to-Cell Transmission of Human T-Cell Lymphotropic Virus Type 1 In Vitro by Carbohydrate-Binding Agents{triangledown}

Emanuela Balestrieri,1 Arianna Ascolani,2 Yasuhiro Igarashi,3 Toshikazu Oki,4 Antonio Mastino,5,6 Jan Balzarini,7 and Beatrice Macchi2,8*

Department of Experimental Medicine and Biochemical Sciences,1 Department of Neuroscience, University of Rome "Tor Vergata," Rome, Italy,2 Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan,3 Keck School of Medicine, University of Southern California, Los Angeles, California,4 Department of Life Sciences, Section of Microbiological, Genetic and Molecular Sciences, University of Messina, Messina, Italy,5 IRCCS, Centro Neurolesi "Bonino-Pulejo," Messina, Italy,6 Rega Institute for Medical Research, K. U. Leuven, Leuven, Belgium,7 IRCCS, S. Lucia, Rome, Italy8

Received 27 December 2007/ Returned for modification 11 February 2008/ Accepted 17 May 2008

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.

* Corresponding author. Mailing address: Department of Neuroscience, University of Rome "Tor Vergata," Via Montpellier 1, 00135 Rome, Italy. Phone: 39 06 72596392. Fax: 39 06 20427282. E-mail: macchi{at}med.uniroma2.it

{triangledown} Published ahead of print on 27 May 2008.

Antimicrobial Agents and Chemotherapy, August 2008, p. 2771-2779, Vol. 52, No. 8
0066-4804/08/$08.00+0     doi:10.1128/AAC.01671-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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