Easterbrook M D, Levy M H, Gomez A M, Turco S J, Epand R M, Rosenthal K L
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 15;10(5):496-505.
In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is associated with a more rapid decline of CD4+ cells and progression to AIDS. Agents that inhibit either virus infection or syncytia formation have the potential to be therapeutically useful. Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania, was recently shown to be a potent nonspecific inhibitor of viral membrane fusion. In this study, LPG demonstrated a dose-dependent inhibition of HIV-1-induced syncytia formation in CD4+ MT-2 cells infected with distinct SI isolates. Fragments of LPG were used to show that inhibition of syncytia formation was dependent on the length of the LPG fragment. Treatment of CD4+ cells or HIV-1 isolates with LPG inhibited infection in vitro. Furthermore, LPG inhibited the replication of SI viral isolates in CD4+ T cells in vitro. LPG had no toxic effects on peripheral blood mononuclear cells at the highest concentrations used in these assays. Further, LPG rapidly associated with the surface membrane of a human T cell line and subsequently disassociated over a 24-h period. The development of compounds capable of inhibiting HIV-induced syncytia formation should provide novel therapeutic approaches to control the spread of virus and disease progression.
在HIV-1感染中，诱导合胞体形成（SI）的毒株的出现与CD4+细胞更快减少以及病情进展至艾滋病相关。抑制病毒感染或合胞体形成的药物具有治疗用途的潜力。脂磷壁酸聚糖（LPG）是利什曼原虫的主要糖缀合物，最近被证明是一种有效的病毒膜融合非特异性抑制剂。在本研究中，LPG在感染不同SI毒株的CD4+ MT-2细胞中表现出对HIV-1诱导的合胞体形成的剂量依赖性抑制。LPG片段用于表明合胞体形成的抑制取决于LPG片段的长度。用LPG处理CD4+细胞或HIV-1毒株可在体外抑制感染。此外，LPG在体外抑制SI病毒毒株在CD4+ T细胞中的复制。在这些试验中使用的最高浓度下，LPG对外周血单核细胞没有毒性作用。此外，LPG迅速与人T细胞系的表面膜结合，随后在24小时内解离。能够抑制HIV诱导的合胞体形成的化合物的开发应能提供控制病毒传播和疾病进展的新治疗方法。
