BIOLOGY OF HUMAN AIDS RETROVIRUS

本项目旨在研究HIV感染的细胞嗜性。 最初，我们开发了一种病灶感染性试验，使用塑料粘附 CD 4阳性HeLa细胞作为体外HIV感染的靶细胞。 随后，该方法被用于研究人类胶质瘤和鳞状细胞癌， 表达与HeLa细胞相同的CD 4载体的癌细胞系。 令人惊讶的是，这些其他细胞系不能直接被HIV感染。 这种传染性的阻断被发现是在病毒进入点 因为细胞在转染病毒DNA后产生了感染性HIV 或感染由嗜酸性鼠白血病病毒假型化的HIV。 这些结果表明，除CD 4外，其他细胞分子也是 这是HIV融合和进入靶细胞所必需的。 使用CD 4阳性HeLa细胞的新克隆进行了额外的工作 检测感染性HIV在血清阳性人血细胞中的表达 患者 结果表明，HIV感染性在非常高的 低水平，最多1/10，000外周血单核细胞 细胞 新克隆的HeLa细胞对 感染比以前的克隆，和艾滋病毒分离，从95%的病人可以 在这些细胞中检测到。 然而，来自5%患者的病毒没有感染 CD 4阳性HeLa细胞。 目前对这些分离株的研究表明， 它们可能是嗜巨噬细胞病毒株。

This project is aimed at studying cell tropism of HIV infectivity in vitro. Initially we developed a focal infectivity assay using plastic-adherent CD4-positive HeLa cells as targets for HIV infection in vitro. Subsequently this approach was used to study human glioma and squamous cell carcinoma cell lines expressing the same CD4 vector as the HeLa cells. Surprisingly these other cell lines could not be infected directly by HIV. This block in infectivity was found to be at the point of viral entry because the cells produced infectious HIV after transfection with viral DNA or infection with HIV pseudotyped by amphotropic murine leukemia virus. These results indicate that other cellular molecules in addition to CD4 are required for HIV fusion and entry into target cells. Additional work has been done using a new clone of CD4-positive HeLa cells to assay expression of infectious HIV in blood cells of seropositive human patients. The results indicated that HIV infectivity was expressed at very low levels, up to a maximum of 1 in 10,000 peripheral blood mononuclear cells. The new clone of HeLa cells was 300-fold more sensitive to infection than previous clones, and HIV isolates from 95% patients could be detected in these cells. However, virus from 5% of patients did not infect the CD4-positive HeLa cells. Current work on these isolates suggests that they are probably macrophage-tropic virus strains.