A model system for human cytomegalovirus-mediated modulation of human immunodeficiency virus type 1 long terminal repeat activity in brain cells

T N Moreno; E A Fortunato; K Hsia; S A Spector; D H Spector

doi:10.1128/JVI.71.5.3693-3701.1997

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A model system for human cytomegalovirus-mediated modulation of human immunodeficiency virus type 1 long terminal repeat activity in brain cells

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A model system for human cytomegalovirus-mediated modulation of human immunodeficiency virus type 1 long terminal repeat activity in brain cells

T N Moreno, E A Fortunato, K Hsia, S A Spector and D H Spector

Journal of virology, Vol.71(5), pp.3693-3701

05/1997

DOI: https://doi.org/10.1128/JVI.71.5.3693-3701.1997

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https://hdl.handle.net/2376/110123

PMCID: PMC191518

PMID: 9094643

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Abstract

Cytomegalovirus - genetics

Brain - virology

Transcription, Genetic

HIV Long Terminal Repeat

Tumor Cells, Cultured

HIV-1 - genetics

Cytomegalovirus - physiology

Gene Expression

DNA Replication

Previously, our laboratory showed that human cytomegalovirus (HCMV) activates human immunodeficiency virus type 1 (HIV-1) in brain-derived cells with limited HIV-1 gene expression but inhibits HIV-1 in cells fully permissive for replication of both viruses (F. M. Jault, S. A. Spector, and D. H. Spector, J. Virol. 68:959-973, 1994). To investigate these effects further, we developed a model system that uncouples HIV-1 gene expression from long terminal repeat (LTR) activity. Two monoclonal U373-MG astrocytoma/glioblastoma cell lines (LTRIG and LIGHIVDC) were generated, each containing an integrated copy of an LTR-chloramphenicol acetyltransferase (CAT) construct and the Escherichia coli lacI gene. LIGHIVDC also has an inducible HIV-1 genome controlled by a Rous sarcoma virus promoter with lac operator sequences. Basal LTR-mediated CAT activity is 65-fold higher in LIGHIVDC than in LTRIG, and this activity is further increased (20-fold) following incubation of LIGHIVDC with isopropyl-beta-D-thiogalactopyranoside (IPTG). Tat protein can be detected by immunostaining in LIGHIVDC. However, Rev-mediated transport and subsequent translation of the singly spliced and unspliced HIV-1 mRNAs is inefficient. In the absence of Tat, HCMV stimulated CAT activity approximately 20-fold, and this activation required HCMV gene expression but not viral DNA replication. LTR-directed transcription was unaffected by HCMV infection in LIGHIVDC but was inhibited in these cells when they contained increased Tat levels following IPTG induction. These results support the hypothesis that HCMV can induce the HIV-1 LTR when HIV-1 gene expression is minimal and that a threshold level of HIV-1 gene products is necessary for HCMV to inhibit this promoter.

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Title: A model system for human cytomegalovirus-mediated modulation of human immunodeficiency virus type 1 long terminal repeat activity in brain cells
Creators: T N Moreno - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
E A Fortunato
K Hsia
S A Spector
D H Spector
Publication Details: Journal of virology, Vol.71(5), pp.3693-3701
Academic Unit: School of Molecular Biosciences
Publisher: United States
Grant note: AI28270 / NIAID NIH HHS
Identifiers: 99900547249001842
Language: English
Resource Type: Journal article