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Journal of Virology, March 2003, p. 3505-3515, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3505-3515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Measles Virus Infects and Suppresses Proliferation of T Lymphocytes from Transgenic Mice Bearing Human Signaling Lymphocytic Activation Molecule

Bumsuk Hahm,1 Nathalie Arbour,1 Denise Naniche,1 Dirk Homann,1 Marianne Manchester,2 and Michael B. A. Oldstone1*

Division of Virology, Department of Neuropharmacology,1 Department of Cell Biology, The Scripps Research Institute, La Jolla, California 920372

Received 1 October 2002/ Accepted 12 December 2002

Humans are the only natural reservoir of measles virus (MV), one of the most contagious viruses known. MV infection and the profound immunosuppression it causes are currently responsible for nearly one million deaths annually. Human signaling lymphocytic activation molecule (hSLAM) was identified as a receptor for wild-type MV as well as for MV strains prepared as vaccines. To better evaluate the role of hSLAM in MV pathogenesis and MV-induced immunosuppression, we created transgenic (tg) mice that expressed the hSLAM molecule under the control of the lck proximal promoter. hSLAM was expressed on CD4+ and CD8+ T cells in the blood and spleen and also on CD4+, CD8+, CD4+ CD8+, and CD4- CD8- thymocytes. Wild-type MV, after limited passage on B95-8 marmoset B cells, and the Edmonston laboratory strain of MV infected hSLAM-expressing cells. There was a direct correlation between the amount of hSLAM expressed on the cells' surface and the degree of viral infection. Additionally, MV infection induced downregulation of receptor hSLAM and inhibited cell division and proliferation of hSLAM+ but not hSLAM- T cells. Therefore, these tg mice provide the opportunity for analyzing and comparing MV-T cell interactions and MV pathogenesis in cells expressing only the hSLAM MV receptor with those of tg mice whose T cells selectively express another MV receptor, CD46.

* Corresponding author. Mailing address: Division of Virology, Department of Neuropharmacology, Mailcode: IMM-6, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8054. Fax: (858) 784-9981. E-mail: mbaobo{at}scripps.edu.

Journal of Virology, March 2003, p. 3505-3515, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3505-3515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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