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Journal of Virology, November 2003, p. 11745-11753, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11745-11753.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Oligodendrocyte-Specific Expression of Human Immunodeficiency Virus Type 1 Nef in Transgenic Mice Leads to Vacuolar Myelopathy and Alters Oligodendrocyte Phenotype In Vitro

Fatiha Radja,1 Denis G. Kay,1* Steffen Albrecht,2 and Paul Jolicoeur1,3,4*

Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7,1 Departments of Pathology,2 Experimental Medicine, McGill University, Montreal, Quebec H3G 1A4,3 Department of Microbiology and Immunology, Université de Montréal, Montreal, Quebec H3C 3J7, Canada4

Received 18 April 2003/ Accepted 23 July 2003

Vacuolar myelopathy (VM) is a frequent central nervous system complication of human immunodeficiency virus type 1 (HIV-1) infection. We report here that transgenic (Tg) mice expressing even low levels of Nef in oligodendrocytes under the regulation of the myelin basic protein (MBP) promoter (MBP/HIVNef) developed VM similar to the human disease in its appearance and topography. The spinal cords of these Tg mice showed lower levels of the myelin proteins MAG and CNPase and of the 21-kDa isoform of MBP prior to the development of vacuoles. In addition, Tg oligodendrocytes in primary in vitro cultures appeared morphologically more mature but, paradoxically, exhibited a less mature phenotype based on O4, O1, CNPase, and MBP staining. In particular, mature CNPase+ MBP+ Tg oligodendrocytes were less numerous than non-Tg oligodendrocytes. Therefore, Nef appears to affect the proper differentiation of oligodendrocytes. These data suggest that even low levels of Nef expression in human oligodendrocytes may be responsible for the development of VM in HIV-1-infected individuals.

* Corresponding author. Mailing address: Clinical Research Institute of Montreal, 110 Pine Ave. West, Montreal, Quebec, Canada H2W 1R7. Phone for Paul Jolicoeur: (514) 987-5569. Fax: (514) 987-5794. E-mail: jolicop{at}ircm.qc.ca. Phone for Denis G. Kay: (514) 987-5570. Fax: (514) 987-5794. E-mail: kayd{at}ircm.qc.ca.

Journal of Virology, November 2003, p. 11745-11753, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11745-11753.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rahim, M. M. A., Chrobak, P., Hu, C., Hanna, Z., Jolicoeur, P. (2009). Adult AIDS-Like Disease in a Novel Inducible Human Immunodeficiency Virus Type 1 Nef Transgenic Mouse Model: CD4+ T-Cell Activation Is Nef Dependent and Can Occur in the Absence of Lymphophenia. J. Virol. 83: 11830-11846 [Abstract] [Full Text]  
  • Hu, C., Dievart, A., Lupien, M., Calvo, E., Tremblay, G., Jolicoeur, P. (2006). Overexpression of Activated Murine Notch1 and Notch3 in Transgenic Mice Blocks Mammary Gland Development and Induces Mammary Tumors. Am. J. Pathol. 168: 973-990 [Abstract] [Full Text]  


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