Role of the Human Cytomegalovirus Major Immediate-Early Promoter's 19-Base-Pair-Repeat Cyclic AMP-Response Element in Acutely Infected Cells

M. J Keller; D. G Wheeler; E Cooper; J. L Meier

doi:10.1128/JVI.77.12.6666-6675.2003

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Role of the Human Cytomegalovirus Major Immediate-Early Promoter's 19-Base-Pair-Repeat Cyclic AMP-Response Element in Acutely Infected Cells

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Role of the Human Cytomegalovirus Major Immediate-Early Promoter's 19-Base-Pair-Repeat Cyclic AMP-Response Element in Acutely Infected Cells

M. J Keller, D. G Wheeler, E Cooper and J. L Meier

Journal of virology, Vol.77(12), pp.6666-6675

06/15/2003

DOI: 10.1128/JVI.77.12.6666-6675.2003

PMCID: PMC156166

PMID: 12767986

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Abstract

ABSTRACT Prior studies have suggested a role of the five copies of the 19-bp-repeat cyclic AMP (cAMP)-response element (CRE) in major immediate-early (MIE) promoter activation, the rate-limiting step in human cytomegalovirus (HCMV) replication. We used two different HCMV genome modification strategies to test this hypothesis in acutely infected cells. We report the following: (i) the CREs do not govern basal levels of MIE promoter activity at a high or low multiplicity of infection (MOI) in human foreskin fibroblast (HFF)- or NTera2-derived neuronal cells; (ii) serum and virion components markedly increase MIE promoter-dependent transcription at a low multiplicity of infection (MOI), but this increase is not mediated by the CREs; (iii) forskolin stimulation of the cAMP signaling pathway induces a two- to threefold increase in MIE RNA levels in a CRE-specific manner at a low MOI in both HFF- and NTera2-derived neuronal cells; and (iv) the CREs do not regulate basal levels of HCMV DNA replication at a high or low MOI in HFF. Their presence does impart a forskolin-induced increase in viral DNA replication at a low MOI but only when basal levels of MIE promoter activity are experimentally diminished. In conclusion, the 19-bp-repeat CREs add to the robust MIE promoter activity that occurs in the acutely infected stimulated cells, although the CREs' greater role may be in other settings.

Details

Title: Subtitle: Role of the Human Cytomegalovirus Major Immediate-Early Promoter's 19-Base-Pair-Repeat Cyclic AMP-Response Element in Acutely Infected Cells
Creators: M. J Keller - Department of Internal Medicine and the Helen C. Levitt Center for Viral Pathogenesis and Disease, University of Iowa Carver College of Medicine
D. G Wheeler - Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada
E Cooper - Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada
J. L Meier - Department of Internal Medicine and the Helen C. Levitt Center for Viral Pathogenesis and Disease, University of Iowa Carver College of Medicine, Veterans Administration Medical Center, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: Journal of virology, Vol.77(12), pp.6666-6675
DOI: 10.1128/JVI.77.12.6666-6675.2003
PMID: 12767986
PMCID: PMC156166
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Language: English
Date published: 06/15/2003
Academic Unit: Infectious Diseases; Epidemiology; Internal Medicine
Record Identifier: 9984094619002771

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