Effects of recombinant soluble CD4 (rCD4) on HIV-1 infection of monocyte/macrophages

Recombinant soluble CD4 (rCD4) was tested for its ability to block acute human immunodeficiency virus (HIV) infection in the U937 monocytic cell line and in human pulmonary alveolar macrophages (PAM) and for its ability to prevent transfer of virus from chronically infected PAM to target peripheral blood mononuclear leukocytes (PMNL). With an initial virus inoculum of 10(3)-10(4) TCID50/ml, rCD4 completely prevented acute HIV infection of U937 cells at concentrations greater than or equal to 1 microgram/ml and provided substantial but incomplete protection at 0.1 microgram/ml. With an initial virus inoculum of 10(2) TCID50/ml, rCD4 completely prevented acute infection of PAM at concentrations greater than or equal to 0.1 microgram/ml. The transmission of HIV-1 infection to PMNL cocultured with chronically infected PAM was completely inhibited at concentrations greater than or equal to 1 microgram/ml if cell-to-cell contact was prevented. With direct PAM-PMNL contact, substantial inhibition was obtained at an rCD4 concentration of 10 micrograms/ml, and higher concentrations (200 micrograms/ml) could completely block transfer. These results demonstrated that rCD4 can be effective in preventing de novo infection of cells of the monocyte/macrophage lineage, but microenvironments where cell-to-cell contact predominates are likely to pose a formidable challenge to this therapeutic strategy.