FAILURE OF HUMAN IMMUNODEFICIENCY VIRUS ENTRY AND INFECTION IN CD4-POSITIVE HUMAN-BRAIN AND SKIN CELLS
FAILURE OF HUMAN IMMUNODEFICIENCY VIRUS ENTRY AND INFECTION IN CD4-POSITIVE HUMAN-BRAIN AND SKIN CELLS
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DOI：
10.1128/jvi.64.1.215-221.1990
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发表时间：
1990-01-01
影响因子：
5.4
通讯作者：
WEHRLY, K
中科院分区：
文献类型：
--
作者：
CHESEBRO, B;BULLER, R;WEHRLY, K
人类细胞上的CD 4分子作为人类免疫缺陷病毒（HIV）的主要受体发挥作用;然而，某些CD 4阴性细胞类型也可能易受感染。因此，我们试图通过使用逆转录病毒载体来定量HIV感染和引入CD 4基因前后人细胞系上的CD 4表达之间的关系。在引入CD 4表达载体之前，通过对所有三种研究的细胞类型的灵敏的焦点免疫测定检测到低水平的HIV感染。在表达不同水平的CD 4的人宫颈癌（HeLa）细胞克隆中有几种HIV毒株，HIV滴度随着CD 4表达的增加而增加。相反，在鳞状细胞癌细胞（SCL 1）和星形胶质细胞（U87 MG），即使高水平的CD 4表达未能增加HIV感染。在这两种细胞系中表达的CD 4蛋白具有预期的分子量，并且能够结合HIV病毒粒子。然而，与CD 4阳性HeLa细胞相反，当与表达HIV包膜蛋白的细胞一起培养时，CD 4阳性U87 MG和SCL 1细胞不能形成合胞体。因此，HIV不能感染这些细胞似乎是由于HIV病毒体包膜蛋白和CD 4阳性细胞膜之间缺乏融合。当细胞被HIV感染时，这种感染性的阻断被克服了，HIV是用嗜酸性鼠白血病病毒的包膜蛋白假型化的。因此，除了CD 4之外，其他细胞表面分子似乎是HIV成功进入和感染这两种人类细胞系所必需的。
CD4 molecules on human cells function as a major receptor for human immunodeficiency virus (HIV); however, certain CD4-negative cell types may also be susceptible to infection. Therefore, we attempted to quantitate the relationship between HIV infection and CD4 expression on human cell lines before and after introduction of the CD4 gene by using a retrovirus vector. Prior to introduction of the CD4 expression vector, low levels of HIV infection were detected by a sensitive focal immunoassay on all three cell types studied. With several HIV strains in clones of human cervical carcinoma (HeLa) cells expressing different levels of CD4, HIV titer increased with increasing CD4 expression. In contrast, in squamous cell carcinoma cells (SCL1) and astroglial cells (U87MG), even high levels of CD4 expression failed to augment HIV infection. The CD4 protein expressed in these two cell lines had the expected molecular weight and was capable of binding HIV virions. However, in contrast to CD4-positive HeLa cells, CD4-positive U87MG and SCL1 cells were unable to form syncytia when cultured with cells expressing HIV envelope protein. Thus, the inability of HIV to infect these cells appeared to be due to lack of fusion between HIV virion envelope proteins and CD4-positive cell membranes. This block in infectivity was overcome when cells were infected with HIV which was pseudotyped with the envelope protein of amphotropic murine leukemia virus. Thus, in addition to CD4, other cell surface molecules appear to be required for successful HIV entry into and infection of these two human cell lines.