Littman Laboratory: Lab Members




NICOLAS MANEL EMBO fellow PhD University Montpellier II, France manel@saturn.med.nyu.edu During my PhD I studied the cellular determinants of HTLV (Human T-cell Leukemia Virus) entry in the laboratory of Marc Sitbon in Montpellier, France. While T lymphocytes constitute the major pool of infected cells in infected patients, we initially determined that HTLV receptor expression is not detectable at the surface of resting T lymphocytes (collaboration with Naomi Taylor's group). However, the HTLV receptor is rapidly induced following activation, correlating with T lymphocyte proliferation. We further demonstrated that GLUT1, the major glucose transporter of mammalian cells, is a receptor for HTLV. We showed that GLUT1 binds the HTLV envelope glycoprotein and that GLUT1 is required for HTLV envelope binding to cell surface as well as HTLV envelope-mediated infection. The HTLV envelope inhibits the glucose transport of GLUT1, suggesting new hypothesis of pathogenesis. Finally, we demonstrated that the 6th extracellular loop of GLUT1 is a HTLV envelope binding domain. However this domain is insufficient to mediate infection, and we demonstrated that the addition of loops 1 and 5 and required for infection, indicating that a novel activity, following envelope binding, is harbored by GLUT1. In Dan Littman's lab, I'm investigating the interaction between dendritic cells and HIV, as well as other aspects of dendritic cell biology. Publications Manel N, Battini JL, Taylor N, Sitbon M. HTLV-1 tropism and envelope receptor. Oncogene. 24(39):6016-25. Swainson L, Kinet S, Manel N, Battini JL, Sitbon M, Taylor N. Glucose transporter 1 expression identifies a population of cycling CD4+ CD8+ human thymocytes with high CXCR4-induced chemotaxis. Proc Natl Acad Sci U S A. 102(36):12867-72. Manel N, Battini JL, Sitbon M. Human T cell leukemia virus envelope binding and virus entry are mediated by distinct domains of the glucose transporter GLUT1. J Biol Chem. 2005 280(32):29025-9. Kim FJ, Manel N, Garrido EN, Valle C, Sitbon M, Battini JL. HTLV-1 and -2 envelope SU subdomains and critical determinants in receptor binding. Retrovirology. 2004 1(1):41. Kim FJ, Manel N, Battini JL, Sitbon M. Envelope capture by retroviruses. Med Sci (Paris). 20(10):876-81. Manel N, Taylor N, Kinet S, Kim FJ, Swainson L, Lavanya M, Battini JL, Sitbon M. HTLV envelopes and their receptor GLUT1, the ubiquitous glucose transporter: a new vision on HTLV infection? Front Biosci. 2004 9:3218-41. Sauce D, Mercier P, Battini JL, Ferrand C, Certoux JM, Manel N, Taylor N, Duperrier A, Herve P, Tiberghien P, Robinet E. Preferential retroviral-mediated transduction of EBV- and CMV-specific T cells after polyclonal T-cell activation. Gene Ther. 2004 11(12):1019-22. Manel N, Kinet S, Kim FJ, Taylor N, Sitbon M, Battini JL. GLUT-1 is the receptor of retrovirus HTLV. Med Sci (Paris). 2004 20(3):277-9. Goh WC, Manel N, Emerman M. The human immunodeficiency virus Vpr protein binds Cdc25C: implications for G2 arrest. Virology. 2004 318(1):337-49. Kim FJ, Battini JL, Manel N, Sitbon M. Emergence of vertebrate retroviruses and envelope capture. Virology. 2004 318(1):183-91. Manel N, Kim FJ, Kinet S, Taylor N, Sitbon M, Battini JL. The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Cell. 2003 115(4):449-59. Kim FJ, Manel N, Boublik Y, Battini JL, Sitbon M. Human T-cell leukemia virus type 1 envelope-mediated syncytium formation can be activated in resistant Mammalian cell lines by a carboxy-terminal truncation of the envelope cytoplasmic domain. J Virol. 2003 77(2):963-9. Manel N, Kinet S, Battini JL, Kim FJ, Taylor N, Sitbon M. The HTLV receptor is an early T-cell activation marker whose expression requires de novo protein synthesis. Blood. 2003 101(5):1913-8. Skirball Institute of Biomolecular Medicine 540 First Avenue, NYC 10016 © 2001 New York University Contact the Webmaster Ethics and Disclaimer