CCR5 EXPRESSION CORRELATES WITH SUSCEPTIBILITY OF MATURING MONOCYTES TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

The chemokine receptor CCR5 and to a lesser extent CCR3 and CCR2b have been shown to serve as coreceptors for human immunodeficiency virus t ype 1 (HIV-1) entry into blood-or tissue-derived macrophages. Therefor e, we examined the expression of the chemokine receptors CCR1, CCR2b, CCR3, CCR5, and CXCR4 as RNAs or as membrane-expressed antigens in mon ocytes maturing into macrophages and correlated these results with the susceptibility of macrophages to HIV-1 infection, as measured by thei r concentrations of extracellular p24 antigen and levels of intracellu lar HIV DNA by quantitative PCR. There was little change in levels of CCR1, CCR2b, and CCR5 RNAs. CCR3 RNA and surface antigen were undetect able throughout maturation of adherent monocytes over 10 days. CXCR4 R NA and membrane antigen were strongly expressed in newly adherent mono cytes, but their levels declined at day 7. The amounts of CCR5 RNA rem ained stable, but the amounts of CCR5 antigen increased from undetecta ble to peak levels at day 7 and then declined slightly at day 10. Leve ls of susceptibility to laboratory (HIV-1(BaL)) and clinical strains o f HIV-1 showed parallel kinetics, peaking at day 7 and then decreasing at days 10 to 14. The concordance of levels of HIV DNA and p24 antige n suggested that the changes in susceptibility with monocyte maturatio n were at or immediately after entry and correlated well with CCR5 exp ression and inversely with CXCR4 expression.