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International Immunology, Vol. 5, No. 9, pp. 1067-1073,September 1993
© 1993 Japanese Society for Immunology
Down-regulation of CD4 molecules by the expression of Nef: a quantitative analysis of CD4 antigens on the cell surfaces
Department of Immunology, Kurume University School of Medicine 67 Asahi-machi Kumume City, Fukuoka 830, Japan
1 Department of Parasitology, Kurume University School of Medicine 67 Asahi-machi, Kurume City, Fukuoka 830, Japan
2 Department of Immunology, Medical Institute of Bioregulation, Kyushu University 69, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan
3 The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine 3420 North Broad Street, Philadelphia, PA 19140, USA
Correspondence to: Correspondence to: Yasuhiro Koga
Nef is one of the non-structural genes encoded by human immunodeficiency viruses. The protein product is associated with the cellular and plasma membranes, and is synthesized soon after entry of the virus. However, little is known about its functions relevant to viral replication and cytopathogenesls. CD4 is considered to be a crucial molecule for the signal transduction and maturation of T cells, and also serves as the receptor for HIV-1. It has been suggested that the down-regulation of cell surface CD4 by Nef proteins is somehow controversial. In order to evaluate the effects of Nef on the CD4 molecule, we constructed a CD4+ monocytold cell line in which the HIV-1 nef gene was placed under the transcrlptional control of the human metallothionein IIA promoter. The analysis of this cellular clone showed that CD4 on the cell surface was down-regulated when Nef proteins were induced. The amount of CD4 antigens on the cell surface correlated Inversely with the level of Nef protein expression. This down-regulation of CD4 antigens by Nef was found to occur at the post-translational level. These results showed that the nef gene could modulate the pathophysiology of AIDS by altering the surface CD4 expression.
Keywords: human immunodeficiency virus 1, human metallothionein IIA promoter, U937 cells
Received 19 October 1992, accepted 18 May 1993.
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