Nakashima H, Yoshida O, Baba M, De Clercq E, Yamamoto N
Department of Virology and Parasitology, Yamaguchi University School of Medicine, Japan.
Antiviral Res. 1989 Jun-Jul;11(5-6):233-46. doi: 10.1016/0166-3542(89)90033-8.
Dextran sulphate is a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1). Its anti-HIV-1 activity has been investigated under varying experimental conditions. MT-4 cells were infected with HIV-1 at different multiplicities of infection (MOI), and treated with either dextran sulphate, 3'-azido-2',3'-dideoxythymidine (AZT), or anti-HIV-1 serum obtained from an ARC patient. Dextran sulphate suppressed HIV-1 replication (as monitored by viral antigen expression) when the MOI was 0.01 or 0.1. It was ineffective at an MOI of 1.0. The anti-HIV-1 serum was only partially effective at an MOI of 0.01 and ineffective at an MOI of 0.1 or 1.0. AZT proved effective at all three MOIs. Co-cultures of uninfected and HIV-1-infected MT-4 cells were protected against destruction by dextran sulphate at a concentration of 10 and 100 micrograms/ml. To fully suppress viral antigen expression a concentration of 100 micrograms/ml was needed. When used at this concentration, a 1-h contact of dextran sulphate with the cells during the virus adsorption period sufficed to suppress HIV-1 antigen expression. In this sense, dextran sulphate behaved like the anti-HIV-1 serum. Dextran sulphate also behaved like OKT-4A in that they both inhibited HIV-1 attachment to the MT-4 cells, whereas OKT-4 failed to do so. However, dextran sulphate did not affect the binding of OKT-4A to the cells. The present results support the concept that dextran sulphate owes its anti-HIV-1 activity mainly to inhibition of virus binding to its target cells. The anti-HIV-1 activity of dextran sulphate is highly dependent on its sulphate content.
硫酸葡聚糖是一种强效且具有选择性的1型人类免疫缺陷病毒(HIV-1)抑制剂。已在不同实验条件下对其抗HIV-1活性进行了研究。用不同感染复数(MOI)的HIV-1感染MT-4细胞,并用硫酸葡聚糖、3'-叠氮-2',3'-双脱氧胸苷(AZT)或从一名艾滋病相关综合征(ARC)患者获得的抗HIV-1血清进行处理。当MOI为0.01或0.1时,硫酸葡聚糖可抑制HIV-1复制(通过病毒抗原表达监测)。在MOI为1.0时无效。抗HIV-1血清在MOI为0.01时仅部分有效,在MOI为0.1或1.0时无效。AZT在所有三种MOI下均证明有效。未感染和HIV-1感染的MT-4细胞共培养物在硫酸葡聚糖浓度为10和100微克/毫升时可免受破坏。要完全抑制病毒抗原表达,需要100微克/毫升的浓度。当以该浓度使用时,在病毒吸附期硫酸葡聚糖与细胞接触1小时就足以抑制HIV-1抗原表达。从这个意义上说,硫酸葡聚糖的表现与抗HIV-1血清相似。硫酸葡聚糖的表现也与OKT-4A相似,因为它们都能抑制HIV-1附着于MT-4细胞,而OKT-4则不能。然而,硫酸葡聚糖并不影响OKT-4A与细胞的结合。目前的结果支持这样一种观点,即硫酸葡聚糖的抗HIV-1活性主要归因于对病毒与其靶细胞结合的抑制。硫酸葡聚糖的抗HIV-1活性高度依赖于其硫酸酯含量。