Coombe D R, Harrop H A, Watton J, Mulloy B, Barrowcliffe T W, Rider C C
Institute for Child Health Research, Perth, Western Australia.
AIDS Res Hum Retroviruses. 1995 Nov;11(11):1393-6. doi: 10.1089/aid.1995.11.1393.
Heparin is a potent inhibitor of HIV-1 replication, in addition to being a well-established inhibitor of blood coagulation. The major anticoagulant activity of heparin results from binding to the plasma protein antithrombin (AT). The high-affinity binding site for AT is a specific pentasaccharide sequence that is of low abundance and completely absent from the majority of heparin chains. We have examined the anti-HIV-1 activity of both conventional and low molecular weight heparins fractionated according to affinity for AT. The high- and low-affinity fractions, despite differing markedly in anticoagulant activity, are identical in their ability to bind to the envelope glycoprotein of HIV-1, and in their inhibitory effect on HIV-1 replication in vitro (EC50 1 and 8 micrograms/ml for conventional and low molecular weight fractions, respectively). Our study shows that the anti-HIV activity of heparin is independent of its antithrombin-mediated inhibition of coagulation proteases. Therefore, heparin preparations retaining full anti-HIV-1 activity in vitro but with greatly reduced anticoagulant activity may be readily produced for further clinical investigation in the prophylaxis and therapy of HIV infection.
肝素不仅是一种公认的血液凝固抑制剂，还是HIV-1复制的有效抑制剂。肝素的主要抗凝活性源于其与血浆蛋白抗凝血酶（AT）的结合。AT的高亲和力结合位点是一种特定的五糖序列，其丰度较低，且大多数肝素链中完全不存在。我们研究了根据对AT的亲和力分级的传统肝素和低分子量肝素的抗HIV-1活性。高亲和力和低亲和力级分尽管抗凝活性差异显著，但它们与HIV-1包膜糖蛋白的结合能力以及对HIV-1体外复制的抑制作用相同（传统级分和低分子量级分的EC50分别为1和8微克/毫升）。我们的研究表明，肝素的抗HIV活性与其抗凝血酶介导的凝血蛋白酶抑制作用无关。因此，有可能很容易制备出在体外保留完全抗HIV-1活性但抗凝活性大大降低的肝素制剂，用于HIV感染预防和治疗的进一步临床研究。
