HIV Replication in CD4-Negative Cell Lines: Effect of Cloning, CD4 Expression and Inhibition by Dextrin Sulphate

Abstract

HIV-1 infects CD4 negative (CD4) cell lines with low efficiency. Infected CD4 cells have a low copy number of HIV proviruses per cell and require a high multiplicity of infection. Following CD4 transfection, most human cell lines permit high efficiency HIV entry and replication. We have compared entry and inhibition of HIV-1 into CD4 cells and their equivalent CD4 positive (CD4+) transfectants. Entry of HIV-1 into both CD4+ and CD4− was completely inhibited by a novel sulphated polysaccharide, dextrin sulphate (DS) at 100 μg ml−1, whereas anti-CD4 antibodies only inhibited HIV infection of CD4+ cells. One glial cell line, U251SP-CD4, expressed surface CD4, but this did not increase HIV-1 susceptibility compared to the CD4− U251SP cell line. Subclones of the CD4− cell lines TE671 and U251SP were no more permissive for infection than their corresponding parental line. HIV-1 infected CD4− cells have a significantly lower provirus copy number than CD4+ cells, confirming that the block to HIV-1 replication is predominantly at entry. The action of DS was examined in conjunction with soluble recombinant CD4 (srCD4); DS was found to potentiate the inhibiting effect of srCD4.