ASSOCIATION OF SIMIAN IMMUNODEFICIENCY VIRUS NEF WITH THE T-CELL RECEPTOR (TCR) ZETA-CHAIN LEADS TO TCR DOWN-MODULATION

The Nef protein of simian immunodeficiency virus (SIV) is dispensable for replication in established T-cell lines but essential for high lev el virus replication in the adult host, though the mechanism by which Nef contributes to this has remained unclear. We demonstrate here that SIV Nef binds to the zeta chain of the T-cell receptor (TCR). SIV Nef proteins that interact with TCR zeta in a yeast two-hybrid system als o reduce T-cell surface expression levels of TCR alpha beta, CD3 and C D4. These findings are the first demonstration that Nef can bind direc tly to a component of the TCR-CD3 complex and modulate its surface exp ression.