This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Radja, F. Articles by Jolicoeur, P. Search for Related Content PubMed PubMed Citation Articles by Radja, F. Articles by Jolicoeur, P.

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

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/HIV^Nef) 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.

This article has been cited by other articles:

• 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]