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几年来 ,HIV 1跨膜蛋白 gp41的生物学功能研究又取得了重大进展 .几个研究小组提供的实验证据证实gp41有一个潜在的细胞受体 .一个重组的gp41胞外区多肽 (aa5 39～ 6 84)以及gp41的免疫抑制多肽 (aa5 83～ 5 99)能够连接人B淋巴细胞和单核细胞 ,仅能较弱的连接T淋巴细胞 .我们发现gp41有 2个细胞结合位点 (aa5 83～ 5 99和aa6 4 1～ 6 75 ) .gp41能够选择性地抑制人T ,B淋巴细胞和单核细胞的增殖 ,选择性地增强人MHCⅠ和Ⅱ类分子以及ICAM Ⅰ分子在细胞表面的表达 .针对第一结合位点的单克隆抗体和 gp41结合蛋白能抑制这种调节作用 .gp41和Ⅰ型干扰素之间存在氨基酸序列的同源性 ,同源区正位于gp41的第一结合位点和Ⅰ型干扰素的受体结合位点 .一些研究结果表明 ,gp41的 2个结合位点与HIV病毒感染细胞相关联 .含有 2个结合位点的多肽分别能够抑制HIV病毒感染细胞 .一个识别第二位点的单抗能广泛中和HIV_1的实验室病毒株和最新分离的病毒株 .此外 ,针对猴免疫缺陷病毒 (SIV)跨膜蛋白 gp32分子上 2个同源区的抗体能保护猴免受SIV的感染 .这些研究结果提示 :gp41细胞结合位点和细胞受体的研究定会对HIV病毒感染机理的研究和疫苗以及抗感染药物的研制产生重大影响 .
In recent years, significant progress has been made in the biological function of the HIV 1 transmembrane protein gp41.Experimental evidence provided by several research groups has confirmed that gp41 has a potential cellular receptor.A recombinant gp41 extracellular domain polypeptide (aa5 39 ~ 6 84) and gp41 immunosuppressive peptides (aa5 83-599) were able to bind to human B lymphocytes and monocytes and only weakly bound T lymphocytes. We found that gp41 has two cell binding sites (aa5 83 ~ 599 and aa6 4 1 ~ 6 75) .Gp41 can selectively inhibit the proliferation of human T, B lymphocytes and monocytes, and selectively enhance the expression of human MHC class Ⅰ and Ⅱ molecules and ICAM Ⅰ molecules on the cell surface .The monoclonal antibody against the first binding site and the gp41 binding protein can inhibit this regulation.The amino acid sequence homology exists between gp41 and type Ⅰ interferon.The orthologous region is located at the first binding site of gp41 And type I interferon receptor binding sites.A number of studies have shown that the two binding sites of gp41 are associated with HIV-infected cells.Polypeptides containing two binding sites are capable of inhibiting the HIV-infected cells, respectively.One recognition second The spot mAb broadly neutralized both the HIV 1 laboratory virus strain and the newly isolated virus strain.In addition, antibodies directed against two homologous regions of the monkey immunodeficiency virus (SIV) transmembrane protein gp32 molecule protected the monkey from SIV These findings suggest that studies of the gp41 cell-binding site and cellular receptors will have a major impact on the mechanisms of HIV infection and on the development of vaccines and anti-infectives.