REPLICATION OF A MACROPHAGE-TROPIC STRAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) IN A HYBRID CELL-LINE, CEMX174, SUGGESTS THAT CELLULAR ACCESSORY MOLECULES ARE REQUIRED FOR HIV-1 ENTRY

To investigate the mechanism underlying one aspect of the cellular tro pism of human immunodeficiency virus type 1 (HIV-1), we used a macroph age-tropic isolate, 89.6, and screened its ability to infect a number of continuous cell lines. HIV-1(89.6) was able to replicate robustly i n a T-cell/B-cell hybrid line, CEMx174, while it replicated modestly o r not at all in either of its parents, one of which is the CD4-positiv e line CEM.3. Analysis by transfection of a molecular clone, a virus u ptake assay, and polymerase chain reaction all provided strong evidenc e that the block to HIV-1(89.6) replication in the CEM.3 line lies at the level of cellular entry. These results were complemented by prepar ing a CD4-expressing derivative of the B-cell parent, 721.174, and dem onstrating that it is permissive for productive HIV-1(89.6) replicatio n. Given these experimental findings, we speculate that there exist ce llular accessory factors which facilitate virus entry and infection in CD4-positive cells. Furthermore, these cellular accessory factors may be quite virus strain specific, since not all macrophage-tropic strai ns of HIV-1 were able to replicate in the CEMx174 hybrid cell line. Th is experimental model provides a system for the identification of one or more of these putative cellular accessory factors.