Tosi P F, Schwartz D, Sharma U, Mouneimne Y, Hannig J, Li G, McKinley G, Grieco M, Flexner C W, Lazarte J, Norse D, Nicolau C, Volsky D J
Center for Blood Research Laboratory and Harvard Medical School, Boston, MA, USA.
Blood. 1996 Jun 1;87(11):4839-44.
Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV-1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.
携带电插入全长CD4的人红细胞(RBC - CD4)可与实验室株1型人类免疫缺陷病毒(HIV - 1)或被HIV - 1感染的T细胞结合并融合。在此我们表明,在来自HIV - 1感染者的外周血单核细胞(PBMC)与未感染PBMC的共培养试验中,RBC - CD4可中和原发性HIV - 1毒株。与单独的红细胞相比,RBC - CD4在这些共培养物中抑制病毒p24核心抗原积累达10000倍。在培养上清液或细胞提取物中进行测量时,病毒p24积累受到同等程度的抑制。这种抑制是剂量依赖性且持久的。同时测试的两种重组CD4在很大程度上无效。在两个独立地点测试的总共23名患者中的21名患者的PBMC培养物中,证实了RBC - CD4在体外对原发性HIV - 1的中和作用。RBC - CD4可能为体内阻断HIV - 1感染提供一条途径。