Jault F M, Spector S A, Spector D H
Department of Biology, University of California, San Diego, La Jolla 92093-0116.
J Virol. 1994 Feb;68(2):959-73. doi: 10.1128/JVI.68.2.959-973.1994.
Human cytomegalovirus (HCMV) is commonly found in the brains of patients with AIDS and in some cases can be detected in the same cells as can human immunodeficiency virus type 1 (HIV-1). In this study, we analyzed the patterns of replication of HIV-1 and HCMV in singly infected cells and the effects of dual infection in human brain-derived cell lines of three different origins: neuroblastoma cell lines SK-N-MC and SY5Y; astrocytoma/glioblastoma cell lines U373-MG and Hs 683; and undifferentiated glioblastoma cell lines A172 and T98G. To bypass the restriction at the adsorption/penetration step in these CD4-negative cells, we used HIV-1 (amphotropic retrovirus) pseudotypes. These HIV-1 pseudotypes infected the majority of the cells in the cultures and expressed high levels of HIV-1 gene products in all except the SY5Y cells. The cell lines differed in the ability to support HCMV infection, but coinfection with HIV-1 had no effect on HCMV replication. The A172 cells were completely nonpermissive for HCMV gene expression, while HCMV replication in the singly infected T98G and SK-N-MC cell lines was restricted at the level of some early gene products. This resulted in complete and partial inhibition, respectively, of viral DNA synthesis. Dual infection of the A172, T98G, and SK-N-MC cells had no effect on HIV-1 replication. The other three cell lines, U373-MG, Hs 683, and SY5Y, were fully permissive for HCMV replication. In the U373-MG and Hs 683 cells, HCMV markedly inhibited the synthesis of HIV-1 gene products. In contrast, a transient stimulation of HIV-1 production followed by a repression was observed in the dually infected SY5Y cells. We conclude from these results that under conditions in which both HIV-1 and HCMV can undergo fully permissive infection, HCMV can repress HIV-1 gene expression. In cells in which HCMV replication is limited but HIV-1 replicates well, there is no effect on HIV-1 gene expression. However, activation of HIV-1, at least transiently, may occur in cells in which HIV-1 gene expression is limited. These studies suggest that a threshold level of some HIV-1 gene product(s) may obscure activation or promote repression of HIV replication by HCMV.
人巨细胞病毒（HCMV）常见于艾滋病患者的大脑中，在某些情况下可在与1型人类免疫缺陷病毒（HIV-1）相同的细胞中检测到。在本研究中，我们分析了HIV-1和HCMV在单一感染细胞中的复制模式，以及双重感染对三种不同来源的人脑源性细胞系的影响：神经母细胞瘤细胞系SK-N-MC和SY5Y；星形细胞瘤/胶质母细胞瘤细胞系U373-MG和Hs 683；以及未分化的胶质母细胞瘤细胞系A172和T98G。为了绕过这些CD4阴性细胞在吸附/穿透步骤的限制，我们使用了HIV-1（嗜性逆转录病毒）假型。这些HIV-1假型感染了培养物中的大多数细胞，并在除SY5Y细胞外的所有细胞中高水平表达HIV-1基因产物。这些细胞系在支持HCMV感染的能力上存在差异，但与HIV-1的双重感染对HCMV复制没有影响。A172细胞对HCMV基因表达完全不敏感，而在单一感染的T98G和SK-N-MC细胞系中，HCMV复制在一些早期基因产物水平受到限制。这分别导致病毒DNA合成的完全和部分抑制。A172、T98G和SK-N-MC细胞的双重感染对HIV-1复制没有影响。其他三个细胞系U373-MG、Hs 683和SY5Y对HCMV复制完全敏感。在U373-MG和Hs 683细胞中，HCMV显著抑制HIV-1基因产物的合成。相反，在双重感染的SY5Y细胞中观察到HIV-1产生先短暂刺激后受到抑制。从这些结果我们得出结论，在HIV-1和HCMV都能进行完全允许性感染的条件下，HCMV可抑制HIV-1基因表达。在HCMV复制受限但HIV-1复制良好的细胞中，对HIV-1基因表达没有影响。然而，在HIV-1基因表达受限的细胞中可能至少短暂地发生HIV-1的激活。这些研究表明，某些HIV-1基因产物的阈值水平可能掩盖激活或促进HCMV对HIV复制的抑制。
