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Journal of Virology, September 2006, p. 8291-8302, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00389-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Use Different Receptor Complexes To Enter T Cells

Kathryn S. Jones,1* Kazunori Fugo,2 Cari Petrow-Sadowski,1 Ying Huang,4 Daniel C. Bertolette,4 Ivonne Lisinski,3 Samuel W. Cushman,3 Steven Jacobson,2 and Francis W. Ruscetti4

Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland 21702,1 Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892,2 Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892,3 Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland 217024

Received 23 February 2006/ Accepted 10 June 2006

Studies using adherent cell lines have shown that glucose transporter-1 (GLUT-1) can function as a receptor for human T-cell leukemia virus type 1 (HTLV). In primary CD4+ T cells, heparan sulfate proteoglycans (HSPGs) are required for efficient entry of HTLV-1. Here, the roles of HSPGs and GLUT-1 in HTLV-1 and HTLV-2 Env-mediated binding and entry into primary T cells were studied. Examination of the cell surface of activated primary T cells revealed that CD4+ T cells, the primary target of HTLV-1, expressed significantly higher levels of HSPGs than CD8+ T cells. Conversely, CD8+ T cells, the primary target of HTLV-2, expressed GLUT-1 at dramatically higher levels than CD4+ T cells. Under these conditions, the HTLV-2 surface glycoprotein (SU) binding and viral entry were markedly higher on CD8+ T cells while HTLV-1 SU binding and viral entry were higher on CD4+ T cells. Binding studies with HTLV-1/HTLV-2 SU recombinants showed that preferential binding to CD4+ T cells expressing high levels of HSPGs mapped to the C-terminal portion of SU. Transfection studies revealed that overexpression of GLUT-1 in CD4+ T cells increased HTLV-2 entry, while expression of HSPGs on CD8+ T cells increased entry of HTLV-1. These studies demonstrate that HTLV-1 and HTLV-2 differ in their T-cell entry requirements and suggest that the differences in the in vitro cellular tropism for transformation and in vivo pathobiology of these viruses reflect different interactions between their Env proteins and molecules on CD4+ and CD8+ T cells involved in entry.

* Corresponding author. Mailing address: Basic Research Program, Bldg. 567, Rm. 253, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702. Phone: (301) 846-5262. Fax: (301) 846-7034. E-mail: joneska{at}mail.nih.gov.

Journal of Virology, September 2006, p. 8291-8302, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00389-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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