DOWN-REGULATION OF CELL-SURFACE CD4 EXPRESSION BY SIMIAN IMMUNODEFICIENCY VIRUS NEF PREVENTS VIRAL SUPER INFECTION

The nef gene product encoded by the mac239 proviral clone of simian im munodeficiency virus (SIV) markedly enhances viral replication and pat hogenesis in vivo. We have used this biologically active nef isolate t o examine the phenotype of Nef in retrovirally transduced human T cell s in culture. SIV Nef is shown to dramatically inhibit cell-surface ex pression of the CD4 glycoprotein without significantly affecting the t otal steady-state level of cellular CD4. This downregulation of the ce ll-surface CD4 receptor for human immunodeficiency virus type 1 (HIV-1 ) infection correlated with the acquisition of resistance to superinfe ction by HIV-1. However, SIV Nef did not affect the level of gene expr ession directed by the HIV-1 long terminal repeat. It is hypothesized that downregulation of cell-surface CD4 by Nef facilitates the efficie nt release of infectious progeny virions and, hence, viral spread in v ivo.