Kitai R, Zhao M L, Zhang N, Hua L L, Lee S C
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
J Neuroimmunol. 2000 Oct 2;110(1-2):230-9. doi: 10.1016/s0165-5728(00)00315-5.
Microglia are the major target of HIV-1 infection in the brain. Microglial infection is CD4-dependent, but the role of chemokine receptors CCR5 and CCR3 and their natural ligands in modulating HIV-1 infection in microglia has been questioned. In primary human fetal microglial cultures, we demonstrate that HIV-1 infection of these cells is dependent on CCR5, since an antibody to CCR5 completely blocked productive infection. Anti-CCR3, in contrast, had a smaller inhibitory effect which was not statistically significant. The chemokine ligands for CCR5, RANTES and MIP-1beta, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1alpha failed to show inhibition. Interestingly, when microglial cultures were treated with antibodies specific to each of these chemokines, HIV-1 infection was enhanced by anti-RANTES and anti-MIP-1beta, but not by anti-MIP-1alpha. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNbeta, a known anti-viral cytokine, also provided potent inhibition of viral infection as well as induction of all three chemokines in microglia. These results suggest the possibility that type I interferon can down-modulate microglial HIV-1 infection in vivo by multiple mechanisms.
小胶质细胞是大脑中HIV-1感染的主要靶细胞。小胶质细胞感染依赖于CD4，但趋化因子受体CCR5和CCR3及其天然配体在调节小胶质细胞中HIV-1感染方面的作用受到质疑。在原代人胎儿小胶质细胞培养中，我们证明这些细胞的HIV-1感染依赖于CCR5，因为一种针对CCR5的抗体完全阻断了有效感染。相比之下，抗CCR3具有较小的抑制作用，且无统计学意义。CCR5的趋化因子配体RANTES和MIP-1β也能有效抑制小胶质细胞中的HIV-1感染，但第三种配体MIP-1α未显示出抑制作用。有趣的是，当用针对这些趋化因子的特异性抗体处理小胶质细胞培养物时，抗RANTES和抗MIP-1β可增强HIV-1感染，而抗MIP-1α则不能。这些结果表明存在内源性趋化因子，它们作为小胶质细胞中HIV-1感染的内源性抑制剂。此外，IFNβ是一种已知的抗病毒细胞因子，它也能有效抑制病毒感染，并诱导小胶质细胞中所有三种趋化因子的产生。这些结果提示I型干扰素可能通过多种机制在体内下调小胶质细胞的HIV-1感染。
