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Journal of Virology, May 2009, p. 5244-5255, Vol. 83, No. 10
0022-538X/09/$08.00+0 doi:10.1128/JVI.02285-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Basic Science Program, SAIC-Frederick, Inc,1 Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, NCI-Frederick, Frederick, Maryland,2 Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Département de Virologie, Institut Pasteur, Paris, France,3 The George Washington University Medical Center, Washington, DC4
Received 31 October 2008/ Accepted 5 March 2009
Little is known about the transmission or tropism of the newly discovered human retrovirus, human T-cell lymphotropic virus type 3 (HTLV-3). Here, we examine the entry requirements of HTLV-3 using independently expressed Env proteins. We observed that HTLV-3 surface glycoprotein (SU) binds efficiently to both activated CD4+ and CD8+ T cells. This contrasts with both HTLV-1 SU, which primarily binds to activated CD4+ T cells, and HTLV-2 SU, which primarily binds to activated CD8+ T cells. Binding studies with heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), two molecules important for HTLV-1 entry, revealed that these molecules also enhance HTLV-3 SU binding. However, unlike HTLV-1 SU, HTLV-3 SU can bind efficiently in the absence of both HSPGs and NRP-1. Studies of entry performed with HTLV-3 Env-pseudotyped viruses together with SU binding studies revealed that, for HTLV-1, glucose transporter 1 (GLUT-1) functions at a postbinding step during HTLV-3 Env-mediated entry. Further studies revealed that HTLV-3 SU binds efficiently to naïve CD4+ T cells, which do not bind either HTLV-1 or HTLV-2 SU and do not express detectable levels of HSPGs, NRP-1, and GLUT-1. These results indicate that the complex of receptor molecules used by HTLV-3 to bind to primary T lymphocytes differs from that of both HTLV-1 and HTLV-2.
Published ahead of print on 11 March 2009.
¶ K.S.J. and R.M. contributed equally to this work.
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