TI  - Efficient interaction of HIV-1 with purified dendritic cells via multiple
      chemokine coreceptors.
PG  - 2433-8
AB  - HIV-1 actively replicates in dendritic cell (DC)-T cell cocultures, but it
      has been difficult to demonstrate substantial infection of purified mature
      DCs. We now find that HIV-1 begins reverse transcription much more
      efficiently in DCs than T cells, even though T cells have higher levels of
      <prot>CD4</prot> and <prot>gp120</prot> binding. DCs isolated from skin or from blood precursors
      behave similarly. Several M-tropic strains and the T-tropic strain IIIB
      enter DCs efficiently, as assessed by the progressive formation of the
      early products of reverse transcription after a 90-min virus pulse at 37
      degrees C. However, few late gag-containing sequences are detected, so
      that active viral replication does not occur. The formation of these early
      transcripts seems to follow entry of HIV-1, rather than binding of virions
      that contain viral DNA. Early transcripts are scarce if DCs are exposed to
      virus on ice for 4 h, or for 90 min at 37 degrees C, conditions which
      allow virus binding. Also the early transcripts once formed are
      insensitive to <prot>trypsin</prot>. The entry of a M-tropic isolates is blocked by the
      chemokine <prot>RANTES</prot>, and the entry of IIIB by SDF-1.  <prot>RANTES</prot>  interacts with
       <prot>CCR5</prot>  and  <prot>SDF-1</prot>  with  <prot>CXCR4</prot>  receptors. Entry of M-tropic but not T-tropic
      virus is ablated in DCs from individuals who lack a functional <prot>CCR5</prot>
      receptor. DCs express more <prot>CCR5</prot> and <prot>CXCR4</prot> mRNA than T cells. Therefore,
      while HIV-1 does not replicate efficiently in mature DCs, viral entry can
      be active and can be blocked by chemokines that act on known receptors for
      M- and T-tropic virus.
AD  - Theodor Kocher Institute, Bern, Switzerland.
