Factors Affecting Human Cytomegalovirus Gene Expression in Human Monocyte Cell Lines

Chan Hee Lee, Gyu Cheol Lee, Yu Jiun Chan, Chuang Jiun Chiou, Jin Hyun Ahn, Gary S. Hayward

Research output: Contribution to journalArticle

Abstract

To understand the mechanisms for establishing and reactivating monocytes and macrophages from latency by human cytomegalovirus (HCMV), human monocyte cell lines were infected and HCMV gene expression was investigated. Indirect immunofluorescence assay (IFA) with monoclonal antibody to HCMV major immediate early (MIE) IE1 or IE2 proteins revealed that HCMV MIE genes were expressed at low levels in relatively more differentiated THP-1 cells with TPA treatment after virus infection (posttreatment). Less differentiated cells such as U937 or HL60 did not support MIE gene expression even after TPA treatment. If THP-1 cells were pretreated before virus infection with TPA and became differentiated at the time of HCMV infection, MIE gene expression increased by 5-6 fold. Therefore, the relative degree of monocyte cell differentiation appears to be an important factor for regulating HCMV gene expression. Further IFA studies using monoclonal antibodies specific for IE1 or IE2 proteins indicate that the sequence and general pattern of IE1 and IE2 gene expression in THP-1 cells treated with TPA were similar to those in permissive human fibroblast cells with some delay in time. Formation of the replication compartment detected with monoclonal antibody to HCMV polymerase accessory protein UL44 in THP-1 cells suggests a fully productive replication process of HCMV in these cells. Monocytes are known to be induced to differentiate by hydrocortisone (HC), tumor necrosis factor (TNF)-α or interferon (IFN)-γ. HC, which is known to stimulate HCMV replication in permissive human fibroblast (HF) cells, enhanced HCMV gene expression by 2-3 fold in TPA-pre or posttreated THP-1 cells, but TNF-α or IFN-γ had little effect. Nitric oxide (NO) is released by immune cells in the defense against foreign stimuli and was shown to inhibit HCMV gene expression in HF cells. Increasing NO by nitroprusside significantly reduced HCMV gene expression in THP-1 cells. Therefore, it appears that the expression of HCMV immediate early genes in THP-1 cells treated with TPA closely resembles those in permissive HF cells.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalMolecules and cells
Volume9
Issue number1
StatePublished - Feb 28 1999

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Keywords

  • Differentiation
  • Gene Expression
  • Human Cytomegalovirus
  • Monocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lee, C. H., Lee, G. C., Chan, Y. J., Chiou, C. J., Ahn, J. H., & Hayward, G. S. (1999). Factors Affecting Human Cytomegalovirus Gene Expression in Human Monocyte Cell Lines. Molecules and cells, 9(1), 37-44.