BIOLOGY OF HUMAN AIDS RETROVIRUS

该项目的重点是研究人类免疫缺陷的能力 病毒（HIV）感染各种人类和小鼠细胞系。CD4基因 编码HIV感染的一个重要受体的基因在 人类和小鼠细胞以及这些细胞对HIV感染易感性 随后使用灵敏的焦点免疫测定（FIA）技术。的 结果表明，在某些人类细胞（HeLa）中的HIV感染是 与不同克隆中CD4表达水平相关。但在 其他人类细胞系，例如U87星形胶质瘤和SCL 1鳞状细胞癌 尽管CD4+细胞非常高，但HIV感染很少成功。 表情进一步的研究表明，艾滋病毒可以结合到CD4上， 这些细胞，但艾滋病毒没有经历成功的融合和进入的细胞， 细胞 这些结果表明，除CD4外，其他细胞分子 是HIV进入细胞所必需的。这种可能性得到了证实， 表明当通常的艾滋病毒进入人体时， 通过使用病毒DNA转染细胞或 感染HIV基因组，通过包装在包膜蛋白中进行假型化， 小鼠逆转录病毒，其使用除CD4以外的受体进入。 类似的实验也使用表达以下蛋白的小鼠细胞系进行： 人CD4。在这些小鼠细胞中，至少有两种水平的 抵抗艾滋病毒感染。第一个是一个类似于U87的条目块 和SCL1人类细胞，但即使通过转染绕过了这一阻断， 或病毒假型化，小鼠细胞仍然具有显著降低的 艾滋病毒感染。目前的数据表明，艾滋病毒表达的减少， 转染的小鼠细胞可能是由于HIV启动子功能差， 在这些小鼠细胞培养物中的增强子序列。

This project has focussed on studying the ability of human immunodeficiency virus (HIV) to infect various human and mouse cell lines. The CD4 gene which encodes an important receptor for HIV infection was expressed in human and mouse cells and susceptibility of these cells to HIV infection was followed using a sensitive focal immunoassay (FIA) technique. The results indicated that HIV infection in certain human cells (HeLa) was related to the level of CD4 expression in different clones. However, in other human lines such as U87 astroglioma and SCL1 squamous cell carcinoma HIV infection was only rarely successful in spite of very high CD4 expression. Further studies indicated that HIV could bind to the CD4 on these cells, but HIV did not undergo successful fusion and entry of the cells. These results suggested that other cellular molecules in addition to CD4 were required for HIV entry of cells. This possibility was confirmed by showing that HIV could infect these human cells when the usual HIV entry mechanisms were bypassed by using viral DNA to tranfect the cells or by infecting with HIV genomes pseudotyped by packaging in envelope proteins of mouse retroviruses which use receptors other than CD4 for entry. Similar experiments were also carried out using mouse cell lines expressing human CD4. In these mouse cells, there were at least two levels of resistance to HIV infection. The first was a block in entry similar to U87 and SCL1 human cells, but even when this block was bypassed by transfection or viral pseudotyping, mouse cells still had a markedly reduced level of HIV infection. Present data suggests that the reduced HIV expression in transfected mouse cells may be due to poor functioning of HIV promotor and enhancer sequences in these mouse cell cultures.