Moulard M, Mabrouk K, Martin I, Van Rietschoten J, Rochat H, Sabatier J M
Centre d'Immunologie de Marseille Luminy, France.
J Pept Res. 1999 Jun;53(6):647-55. doi: 10.1034/j.1399-3011.1999.00062.x.
SPC3, a synthetic multibranched peptide including the GPGRAF consensus motif of the human immunodeficiency virus type 1 (HIV-1) gp120 V3-loop is a potent inhibitor of HIV infection of human CD4+ lymphocytes, macrophages and CD4-/galactosylceramide+ human colon epithelial cells and is currently tested in phase II clinical trials (FDA protocol 257 A). The antiviral property of SPC3 was further investigated for its ability to inhibit LAV-2/B, an HIV-2 clone with a CD4-independent tropism. SPC3 inhibited the LAV-2/B-mediated infection of B-cell line which does not express the CD4 and the galactosylceramide molecules on their cell surface, suggesting an SPC3-sensitive CD4/galactosylceramide-independent pathway of viral infection in HIV susceptible cells. The molecular mechanism of the peptide inhibition was also investigated. The data suggested that the SPC3-mediated inhibition does not result from a direct competition between SPC3 and gp120 binding to the cell surface of the target cell.
SPC3是一种合成的多分支肽，包含人类免疫缺陷病毒1型（HIV-1）gp120 V3环的GPGRAF共有基序，是人类CD4+淋巴细胞、巨噬细胞以及CD4-/半乳糖神经酰胺+人类结肠上皮细胞HIV感染的有效抑制剂，目前正在进行II期临床试验（FDA方案257 A）。对SPC3的抗病毒特性进一步研究了其抑制LAV-2/B的能力，LAV-2/B是一种具有不依赖CD4嗜性的HIV-2克隆。SPC3抑制了不表达细胞表面CD4和半乳糖神经酰胺分子的B细胞系的LAV-2/B介导的感染，提示在HIV易感细胞中存在一条SPC3敏感的不依赖CD4/半乳糖神经酰胺的病毒感染途径。还研究了该肽抑制的分子机制。数据表明，SPC3介导的抑制并非源于SPC3与gp120在靶细胞表面结合之间的直接竞争。
