广谱趋化因子受体结合物-vMIP-II的体内抗SIV功能研究

Anti-SIV Potency of a Broad Spectrum Chemokine Receptors Inhibitor,vMIP-II in vivo

病毒巨噬细胞炎症蛋白II(vMIP-II)是一种广谱趋化因子受体拮抗剂,它所拮抗的趋化因子受体被认为是不同的人免疫缺陷病毒株(Human immunodeficiency virus,HIV)进入靶细胞的辅受体。虽然理论上vMIP-II是一个广谱的HIV抑制剂,但vMIP-II的抗HIV感染作用却少有报道,特别是体内研究。本研究利用一个有效的SIV-mac251感染食蟹猴模型来评价vMIP-II的体内抗HIV感染作用,结果显示vMIP-II能够有效地并呈剂量依赖性地降低食蟹猴血浆病毒载量,同时对宿主免疫功能具有保护作用。这些结果表明vMIP-II是一种有效的抗HIV物质,可以作为一类新型的抗HIV先导药物,也为研发靶向病毒进入的新药提供了进一步的理论支持。

Viral macrophage inflammatory protein Ⅱ （vMIP-Ⅱ） encoded by Human herpesvirus 8 is a potent antagonist of various chemokine receptors, which are believed to be co-receptors for Human immunodeficiency virus （HIV） entry of different strains. Although it is known as a broad-spectrum HIV entry inhibitor, the exact anti-HIV mechansim of vMIP-Ⅱ has been rarely reported, especially in vivo studies. In the present study, the well-established SIVmac251-infected cynomolgus monkey model was used to study the anti-HIV potential of vMIP-Ⅱ in vivo. It was shown that vMIP-Ⅱ caused rapid and significant decrease in plasma viral loads in a dose-dependent manner, which was comparable to that of positive control. Meanwhile, vMIP-Ⅱ was found to protect the host immune function. In summary, these results indicate that vMIP-Ⅱ is a potent anti-HIV agent and provides further rational to develop entry inhibitor.