TI  - <prot>CD4</prot>-induced interaction of primary HIV-1  <prot>gp120</prot>  glycoproteins with the
      chemokine receptor  <prot>CCR-5</prot> .
PG  - 179-83
AB  - For efficient entry into target cells, primary macrophage-tropic and
      laboratory-adapted human immunodeficiency viruses type 1 (HIV-1) require
      particular chemokine receptors, <prot>CCR-5</prot> and <prot>CXCR-4</prot>, respectively, as well as
      the primary receptor <prot>CD4</prot> (refs 1-6). Here we show that a complex of   <prot>gp120</prot>  ,
      the exterior envelope glycoprotein, of macrophage-tropic primary HIV-1 and
      soluble   <prot>CD4</prot>   interacts specifically with  <prot>CCR-5</prot>  and inhibits the binding of
      the natural <prot>CCR-5</prot> ligands,<prot> macrophage inflammatory protein (MIP)-1alpha</prot>
      and <prot>MIP-1beta</prot> (refs 7, 8). The apparent affinity of the interaction
      between  <prot>gp120</prot>  and  <prot>CCR-5</prot>  was dramatically lower in the absence of soluble
      <prot>CD4</prot>. Additionally, in the absence of <prot>gp120</prot>, an interaction between a
      two-domain  <prot>CD4</prot>  fragment and  <prot>CCR-5</prot>  was observed. A  <prot>gp120</prot>  fragment retaining
      the <prot>CD4</prot>-binding site and overlapping epitopes was able to interact with
       <prot>CCR-5</prot>  only if the V3 loop, which can specify HIV-1 tropism and chemokine
      receptor choice, was also present on the molecule. Neutralizing antibodies
      directed against either <prot>CD4</prot>-induced or V3 epitopes on <prot>gp120</prot> blocked the
      interaction of   <prot>gp12O</prot> - <prot>CD4</prot>   complexes with  <prot>CCR-5</prot> . These results suggest that
      HIV-1 attachment to <prot>CD4</prot> creates a high-affinity binding site for <prot>CCR-5</prot>,
      leading to membrane fusion and virus entry.
AD  - LeukoSite, Inc., Cambridge, Massachusetts 02142, USA.
