Oligodendrocyte-specific expression of human immunodeficiency virus type 1 Nef in transgenic mice leads to vacuolar myelopathy and alters oligodendrocyte phenotype in vitro.
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.
Radja
Fatiha
F
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.
Kay
Denis G
DG
Albrecht
Steffen
S
Jolicoeur
Paul
P
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013118:Spinal Cord Diseases / Q000473:pathology / Q000821:virology; D019076:Transgenes; D014617:Vacuoles / Q000648:ultrastructure*
D015693:Gene Products, nef; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases