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

By Fatiha Radja, Denis G. Kay, Steffen Albrecht and Paul Jolicoeur

Abstract

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

Topics: Pathogenesis and Immunity
Publisher: American Society for Microbiology
Year: 2003
DOI identifier: 10.1128/JVI.77.21.11745-11753.2003
OAI identifier: oai:pubmedcentral.nih.gov:229323
Provided by: PubMed Central
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