Relative Inefficiency of Soluble Recombinant CD4 for Inhibition of Infection by Monocyte-Tropic HIV in Monocytes and T Cells
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
Pagination or Media Count:
Macrophages are major viral reservoirs in the brain, lungs, and lymph nodes of HIV-infected patients. But not all HIV isolates infect macrophages. The molecular basis for this restrictive target cell tropism and the mechanisms by which HIV infects macrophages are not well understood virus uptake by CD4- dependent and independent pathways have both been proposed. Soluble rCD4 sCD4 binds with high affinity to gp120, the envelope glycoprotein of HIV, and at relatively low concentrations completely inhibits infection of many HIVstrains in T cells or T cell lines. HTLV-IIIB infection of the H9 T cell line was completely inhibited by prior treatment of virus with 10mgml sCD4 no p24 Ag or HIV-induced t Cell syncytia were detected in cultures of H9 cells exposed to 1 x 104 TCID50 HTLV-IIIB in the presence of sCD4. Under identical conditions and at a 100-fold lower viral inoculum, 10 mgml sCD4 had little or no effect on infection of monocytes by an of six different HIV isolates by three different criteria p24 Ag release, virus-induced cytopathic effects, and the frequency of infected cells that express HIV-specific mRNA. At 10-to 100-fold higher concentrations of sCD4, however, infection was completely inhibited. Monoclonal anti-CD4 for inhibition of HIV infection in monocytes was a property of the virion, not the target cell HIV isolates that infect both monocytes and T cells required similarly high levels of sCD4 100 to 200 mgml for inhibition of infection.
- Medicine and Medical Research