HIV REPLICATION IN CD4-NEGATIVE CELL-LINES - EFFECT OF CLONING, CD4 EXPRESSION AND INHIBITION BY DEXTRIN SULFATE

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 mug 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.