CHEMOKINE RECEPTOR REGULATION AND HIV TYPE-1 TROPISM IN MONOCYTE-MACROPHAGES

Monocyte-macrophages can be productively infected by CCR5-specific, bu t not CXCR4-specific, HIV-1, This could be due either to the absence o f this chemokine receptor in this cell lineage or to other, yet undefi ned cellular cofactors that modulate the coreceptor activity of the CX CR4 in these cells, To investigate the basis of macrophage tropism, we studied the expression of CCRS and CXCR4, as well as several of the o ther CC chemokine receptors, on monocyte-macrophages at different stag es of differentiation. We found that on fresh monocytes, CXCR4 was rel atively abundant, but it fell to barely detectable levels in culture o ver 24 hr and maintained this low level of expression during different iation in vitro, Some donor macrophages appeared to express CXCR4 at l evels comparable to CCRS, In contrast, CCRS expression was low on fres h monocytes but increased on in vitro differentiation. Taken together, the results show that monocyte-macrophage differentiation is associat ed with a differential expression of chemokine receptors that may cont ribute to, but does not fully account for, the selectivity of these ce lls to HIV entry, GM-CSF, a cytokine that induces macrophage different iation, caused a rapid decrease in CXCR4 and CCRS mRNA and was correla ted with decreased ability to support HIV entry.