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PMID: 8627801 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The enhancer domain of the human cytomegalovirus major immediate-early promoter determines cell type-specific expression in transgenic mice.

Journal of virology ·Vol. 70 ·No. 5 ·1996-05-00 ·Pages 3207-14

Baskar JF, Smith PP, Nilaver G, Jupp RA, Hoffmann S, Peffer NJ, Tenney DJ, Colberg-Poley AM, Ghazal P, Nelson JA

Abstract

The human cytomegalovirus (HCMV) major immediate-early promoter (MIEP) is one of the first promoters to activate upon infection. To examine HCMV MIEP tissue-specific expression, transgenic mice were established containing the lacZ gene regulated by the MIEP (nucleotides -670 to +54). In the transgenic mice, lacZ expression was demonstrated in 19 of 29 tissues tested by histochemical and immunochemical analyses. These tissues included brain, eye, spinal cord, esophagus, stomach, pancreas, kidney, bladder, testis, ovary, spleen, salivary gland, thymus, bone marrow, skin, cartilage, and cardiac, striated and smooth muscles. Although expression was observed in multiple organs, promoter activity was restricted to specific cell types. The cell types which demonstrated HCMV MIEP expression included retinal cells of the eye, ductile cells of the salivary gland, exocrine cells of the pancreas, mucosal cells of the stomach and intestine, neuronal cells of the brain, muscle fibers, thecal cells of the corpus luteum, and Leydig and sperm cells of the testis. These observations indicate that the HCMV MIEP is not a pan-specific promoter and that the majority of expressing tissues correlate with tissues naturally infected by the virus in the human host.

MeSH Terms
Animals Central Nervous System/metabolism Cytomegalovirus/genetics Digestive System/metabolism Enhancer Elements, Genetic Female Gene Expression Regulation, Viral Genes, Immediate-Early Humans Lac Operon Male Mice Mice, Transgenic Organ Specificity Promoter Regions, Genetic Urogenital System/metabolism beta-Galactosidase/biosynthesis
Chemicals
beta-Galactosidase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Baskar J F
Department of Molecular Microbiology and Immunology, School of Medicine, Oregon Health Sciences University, Portland 97201, USA.
Smith P P
Nilaver G
Jupp R A
Hoffmann S
Peffer N J
Tenney D J
Colberg-Poley A M
Ghazal P
Nelson J A
References (54)
54 references, click to expand
  1. Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate-early gene region.
    J Virol. 1989 Jun;63(6):2699-708 PMID: 2542583
  2. Retinoid activation of retinoic acid receptors but not of retinoid X receptors promotes cellular differentiation and replication of human cytomegalovirus in embryonal cells.
    J Virol. 1995 Jun;69(6):3831-7 PMID: 7745731
  3. Human cytomegalovirus latent infection of granulocyte-macrophage progenitors.
    Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11879-83 PMID: 7991550
  4. Severe tubulo-interstitial disease in a renal allograft due to cytomegalovirus infection.
    Clin Nephrol. 1982 Dec;18(6):321-5 PMID: 6295675
  5. Cytomegalovirus infection of the alimentary canal: radiologic findings with pathologic correlation.
    Radiology. 1987 May;163(2):317-23 PMID: 3031723
  6. CYTOMEGALIC INCLUSION DISEASE AFFECTING THE TEMPORAL BONE.
    Laryngoscope. 1965 Apr;75:628-38 PMID: 14283784
  7. The cytomegalovirus enhancer: a pan-active control element in transgenic mice.
    Mol Cell Biol. 1990 Aug;10(8):4406-11 PMID: 2164640
  8. The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements.
    J Virol. 1989 Jul;63(7):3026-33 PMID: 2542610
  9. Human cytomegalovirus (HCMV) immediate-early enhancer/promoter specificity during embryogenesis defines target tissues of congenital HCMV infection.
    J Virol. 1995 Apr;69(4):2194-207 PMID: 7884867
  10. Localization of cytomegalovirus proteins and genome during fulminant central nervous system infection in an AIDS patient.
    J Neuropathol Exp Neurol. 1986 Mar;45(2):127-39 PMID: 3005516
  11. Intranuclear and Cytoplasmic Inclusions ("Protozoan-Like Bodies") in the Salivary Glands and Other Organs of Infants.
    Am J Pathol. 1932 Mar;8(2):123-136.3 PMID: 19970004
  12. Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos.
    EMBO J. 1986 Dec 1;5(12):3133-42 PMID: 3102226
  13. Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1.
    J Virol. 1985 Dec;56(3):665-75 PMID: 2999423
  14. Cytomegalovirus oophoritis: ovarian cortical necrosis.
    Hum Pathol. 1977 May;8(3):285-92 PMID: 192660
  15. Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements.
    J Virol. 1992 Jul;66(7):4434-44 PMID: 1318413
  16. Gastrointestinal hemorrhage secondary to cytomegalovirus after renal transplantation. A case report and review of the problem.
    Am J Surg. 1976 Mar;131(3):371-4 PMID: 769586
  17. A STAIN FOR THE HISTOCHEMICAL DEMONSTRATION OF NUCLEIC ACIDS.
    Exp Mol Pathol. 1965 Jun;11:266-74 PMID: 14300112
  18. Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis.
    Am J Pathol. 1988 Oct;133(1):73-81 PMID: 2845792
  19. The variability in activity of the universally expressed human cytomegalovirus immediate early gene 1 enhancer/promoter in transgenic mice.
    Nucleic Acids Res. 1991 Nov 25;19(22):6205-8 PMID: 1956779
  20. Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection.
    J Virol. 1982 Feb;41(2):462-77 PMID: 6281461
  21. Pancreatic islet-cell damage in children with fatal viral infections.
    Lancet. 1980 Aug 16;2(8190):354-8 PMID: 6105486
  22. Infection of hematopoietic progenitor cells by human cytomegalovirus.
    Blood. 1992 Jul 1;80(1):170-8 PMID: 1377049
  23. NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation.
    EMBO J. 1989 Dec 20;8(13):4251-8 PMID: 2556267
  24. Pneumonia as a clinical manifestation of cytomegalovirus infection in previously healthy adults.
    Scand J Infect Dis. 1972;4(1):7-10 PMID: 4336589
  25. Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus.
    Am J Pathol. 1988 Aug;132(2):239-48 PMID: 2840830
  26. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  27. Cell type-specific induction of the major immediate early enhancer of human cytomegalovirus by cyclic AMP.
    J Gen Virol. 1990 Jan;71 ( Pt 1):105-13 PMID: 2154528
  28. Cytomegalovirus but not human T lymphotropic virus type III/lymphadenopathy associated virus detected by in situ hybridisation in retinal lesions in patients with the acquired immune deficiency syndrome.
    Br Med J (Clin Res Ed). 1986 Jul 19;293(6540):162-4 PMID: 3015317
  29. The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements.
    J Virol. 1990 Jan;64(1):264-77 PMID: 2152815
  30. Acquired cytomegalovirus infection in older children and adults. A clinical study of hospitalized patients.
    Scand J Infect Dis. 1970;2(2):95-103 PMID: 4329177
  31. Cytomegalovirus and atherosclerosis.
    Eur Heart J. 1993 Dec;14 Suppl K:30-8 PMID: 8131785
  32. Cytomegalovirus encephalitis in patients with acquired immunodeficiency syndrome: an autopsy study of 30 cases and a review of the literature.
    Hum Pathol. 1987 Mar;18(3):289-97 PMID: 3028930
  33. Negative and positive regulation by a short segment in the 5'-flanking region of the human cytomegalovirus major immediate-early gene.
    Mol Cell Biol. 1987 Nov;7(11):4125-9 PMID: 2828927
  34. Specific interactions between transcription factors and the promoter-regulatory region of the human cytomegalovirus major immediate-early gene.
    J Virol. 1988 Mar;62(3):1076-9 PMID: 2828657
  35. Elevated antibody titers against cytomegalovirus among patients with testicular cancer.
    Int J Cancer. 1988 Mar 15;41(3):399-403 PMID: 2831159
  36. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus.
    Cell. 1985 Jun;41(2):521-30 PMID: 2985280
  37. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169.
    Curr Top Microbiol Immunol. 1990;154:125-69 PMID: 2161319
  38. Multiple sequence-specific transcription factors modulate cytomegalovirus enhancer activity in vitro.
    Mol Cell Biol. 1988 Apr;8(4):1809-11 PMID: 2837656
  39. Promoter-regulatory region of the major immediate early gene of human cytomegalovirus.
    Proc Natl Acad Sci U S A. 1984 Feb;81(3):659-63 PMID: 6322160
  40. The 21bp repeat element of the human cytomegalovirus major immediate early enhancer is a negative regulator of gene expression in undifferentiated cells.
    Nucleic Acids Res. 1991 Apr 25;19(8):1767-71 PMID: 1851560
  41. Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells.
    Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7630-4 PMID: 1323848
  42. Cytomegalovirus infection of ovarian thecoma.
    Arch Pathol Lab Med. 1979 Nov;103(12):653-4 PMID: 228631
  43. Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption.
    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9829-33 PMID: 7568227
  44. Structural analysis of the major immediate early gene of human cytomegalovirus.
    J Virol. 1984 Jan;49(1):190-9 PMID: 6317889
  45. Transcriptional regulation of the human cytomegalovirus major immediate-early gene is associated with induction of DNase I-hypersensitive sites.
    Mol Cell Biol. 1986 Feb;6(2):452-61 PMID: 3023848
  46. Potential role of human cytomegalovirus and p53 interaction in coronary restenosis.
    Science. 1994 Jul 15;265(5170):391-4 PMID: 8023160
  47. Phytohemagglutinin-induced activity of cyclic AMP (cAMP) response elements from cytomegalovirus is reduced by cyclosporine and synergistically enhanced by cAMP.
    J Virol. 1990 May;64(5):2388-91 PMID: 2157893
  48. Repression of human cytomegalovirus gene expression associated with a novel immediate early regulatory region binding factor.
    Nucleic Acids Res. 1989 Nov 25;17(22):9165-71 PMID: 2555785
  49. Cytomegalovirus-associated tubulointerstitial nephritis in an allogeneic bone marrow transplant recipient.
    Ann Intern Med. 1987 Sep;107(3):351-2 PMID: 3039888
  50. Developmental analysis of the cytomegalovirus enhancer in transgenic animals.
    J Virol. 1996 May;70(5):3215-26 PMID: 8627802
  51. Cerebral involvement with advanced periventricular calcification in generalized cytomegalic inclusion disease in the newborn; a clinicopathological report of a case diagnosed during life.
    J Neuropathol Exp Neurol. 1954 Oct;13(4):562-86 PMID: 13201971
  52. Regulation and tissue-specific expression of human cytomegalovirus.
    Curr Top Microbiol Immunol. 1990;154:75-100 PMID: 2161326
  53. Patterns of transcription of human cytomegalovirus in permissively infected cells.
    J Virol. 1980 Aug;35(2):277-86 PMID: 6160258
  54. HIV and HCMV coinfect brain cells in patients with AIDS.
    Virology. 1988 Jul;165(1):286-90 PMID: 2838967
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1996-05-00
Pages
3207-14
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC190184
Subset
IM
Grants
NCI NIH HHS · CA50151 · United States
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