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 type 1 (HIV-1) entry into blood- or tissue-derived macrophages. Therefore, we examined the expression of the chemokine receptors CCR1, CCR2b, CCR3, CCR5, and CXCR4 as RNAs or as membrane-expressed antigens in monocytes maturing into macrophages and correlated these results with the susceptibility of macrophages to HIV-1 infection, as measured by their concentrations of extracellular p24 antigen and levels of intracellular HIV DNA by quantitative PCR. There was little change in levels of CCR1, CCR2b, and CCR5 RNAs. CCR3 RNA and surface antigen were undetectable throughout maturation of adherent monocytes over 10 days. CXCR4 RNA and membrane antigen were strongly expressed in newly adherent monocytes, but their levels declined at day 7. The amounts of CCR5 RNA remained stable, but the amounts of CCR5 antigen increased from undetectable to peak levels at day 7 and then declined slightly at day 10. Levels of susceptibility to laboratory (HIV-1(BaL)) and clinical strains of 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 antigen suggested that the changes in susceptibility with monocyte maturation were at or immediately after entry and correlated well with CCR5 expression and inversely with CXCR4 expression.

现已证实，CC趋化因子受体5（CCR5）以及在较小程度上的CC趋化因子受体3（CCR3）与CC趋化因子受体2b（CCR2b），可作为人类免疫缺陷病毒1型（HIV-1）侵入血液或组织来源巨噬细胞的共受体。为此，我们针对单核细胞向巨噬细胞分化成熟过程中，CC趋化因子受体1（CCR1）、CC趋化因子受体2b（CCR2b）、CC趋化因子受体3（CCR3）、CC趋化因子受体5（CCR5）以及CXC趋化因子受体4（CXCR4）的RNA表达或膜表达抗原情况进行了检测，并将所得结果与巨噬细胞对HIV-1的感染易感性进行关联分析；感染易感性通过细胞外p24抗原浓度以及通过定量聚合酶链式反应（quantitative PCR）检测的细胞内HIV DNA水平进行量化。CC趋化因子受体1、CC趋化因子受体2b及CC趋化因子受体5的RNA水平几乎无变化。在贴壁单核细胞为期10天的成熟过程中，始终未检测到CC趋化因子受体3 RNA及其表面抗原。CXC趋化因子受体4 RNA与膜抗原在新贴壁的单核细胞中呈高表达，但在第7天时其水平出现下降。CC趋化因子受体5 RNA的含量保持稳定，但CC趋化因子受体5抗原的量从无法检出逐步升高至第7天的峰值水平，随后在第10天时略有回落。巨噬细胞对实验室毒株HIV-1(BaL)及临床HIV-1毒株的感染易感性呈现相似的动力学变化趋势：于第7天达到峰值，随后在第10至14天逐渐降低。HIV DNA与p24抗原的水平具有良好的一致性，这表明单核细胞成熟过程中感染易感性的变化发生在病毒侵入阶段或侵入后即刻，且与CC趋化因子受体5的表达呈正相关、与CXC趋化因子受体4的表达呈负相关。