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Journal of Virology, February 2007, p. 1650-1659, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02134-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human Infection{triangledown}

Shinji Ohno,1* Nobuyuki Ono,1,{dagger} Fumio Seki,1,{ddagger} Makoto Takeda,1 Shinobu Kura,2 Teruhisa Tsuzuki,2 and Yusuke Yanagi1

Department of Virology,1 Department of Medical Biophysics and Radiation Biology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan2

Received 29 September 2006/ Accepted 16 November 2006

The human signaling lymphocyte activation molecule (SLAM, also called CD150), a regulator of antigen-driven T-cell responses and macrophage functions, acts as a cellular receptor for measles virus (MV), and its V domain is necessary and sufficient for receptor function. We report here the generation of SLAM knockin mice in which the V domain of mouse SLAM was replaced by that of human SLAM. The chimeric SLAM had an expected distribution and normal function in the knockin mice. Splenocytes from the SLAM knockin mice permitted the in vitro growth of a virulent MV strain but not that of the Edmonston vaccine strain. Unlike in vitro infection, MV could grow only in SLAM knockin mice that also lacked the type I interferon receptor (IFNAR). After intraperitoneal or intranasal inoculation, MV was detected in the spleen and lymph nodes throughout the body but not in the thymus. Notably, the virus appeared first in the mediastinal lymph node after intranasal inoculation. Splenocytes from MV-infected IFNAR–/– SLAM knockin mice showed suppression of proliferative responses to concanavalin A. Thus, MV infection of SLAM knockin mice reproduces lymphotropism and immunosuppression in human infection, serving as a useful small animal model for measles.

* Corresponding author. Mailing address: Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. Phone: 81 92 642 6135. Fax: 81 92 642 6140. E-mail: soono{at}virology.med.kyushu-u.ac.jp.

{triangledown} Published ahead of print on 29 November 2006.

{dagger} Present address: Departments of Immunology and Medical Biophysics, University Health Network, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada.

{ddagger} Present address: Department of Virology 3, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011, Japan.

Journal of Virology, February 2007, p. 1650-1659, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02134-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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