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

The human immunodeficiency virus (HIV) binds to its cellular receptor, CD4. This binding is mediated by the viral surface glycoprotein gpl20, thus initiating viral infection at the cellular level. This process may also be partly responsible for the cytopathic properties of HIV. Regardless of the strain variations encountered within HIV and the differences between HIV-1 and HIV-2, CD4 binding is an essential part of the infectious process. Interruption of the binding process may be a means of altering infection. A soluble, cell-free form of the extracellular part of the CD4 molecule, known as rCD4, was previously shown to bind with HIV in a manner similar to the natural molecule. The bound rCD4 appeared, in earlier studies, to inhibit HIV infection of lymphoid cells. This study examines the effects of rCD4 on acute HIV infection of human pulmonary macrophages (PAM) and monocytes (monocytic U937 cells), and evaluates its ability to interfere with the possible transfer of infection to target lymphocytes. (Monocytes and lymphocytes are types of white blood cells.) The potential of the success of these effects is in the treatment of HIV infections such as AIDS. The rCD4 was capable of preventing infection of PAM cells at concentrations greater than or equal to 1 microgram per milliliter. The same concentration inhibited the transmission of HIV-1 to peripheral blood mononuclear leucocytes (PMNL) cultured together with chronically infected PAM in the absence of cell contact. With cell contact, rCD4 concentrations of 10 micrograms per milliliter produced substantial inhibition; transfer was completely blocked at higher concentrations. The potential value of rCD4 as a tool in the antiretrovirus efforts requires further study