A mechanism of resistance to HIV-1 entry: Inefficient interactions of CXCR4 with CD4 and gp120 in macrophages

To test the hypothesis that inefficient interactions of CXCR4 with CD4 and gp120 could affect HIV-1 entry, we incubated macrophages, monocytes, and ly mphocytes with gp120 and coimmunoprecipitated CD4 by using anti-CXCR4 antib odies. CD4 was efficiently coimmunoprecipitated in lymphocytes and monocyte s but not in macrophages. Overexpression of CD4 in macrophages resulted in detection of CD4-CXCR4 and gp120-CD4-CXCR4 complexes in parallel with the r estoration of macrophage fusion susceptibility. These results suggest a mec hanism of resistance to entry of some X4 HIV-1 strains into macrophages and a method for dissection of the initial stages of HIV entry.