The effects of cytomegalovirus on human immunodeficiency virus replication in brain-derived cells correlate with permissiveness of the cells for each virus.
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.
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Department of Biology, University of California, San Diego, La Jolla 92093-0116.
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D000956:Antigens, Viral / Q000096:biosynthesis; D001254:Astrocytoma / Q000382:microbiology; D001921:Brain / Q000166:cytology / Q000382:microbiology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000254:growth & development* / Q000302:isolation & purification; D004261:DNA Replication; D005909:Glioblastoma / Q000382:microbiology; D015497:HIV-1 / Q000145:classification / Q000254:growth & development* / Q000302:isolation & purification; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000382:microbiology; D015163:Superinfection; D014764:Viral Proteins / Q000032:analysis / Q000096:biosynthesis; D014771:Virion / Q000254:growth & development; D014779:Virus Replication
D000956:Antigens, Viral; D017874:Immediate-Early Proteins; D014764:Viral Proteins; C044582:immediate-early proteins, cytomegalovirus