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Cytomegalovirus and Macrophage Interaction

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Molecular Aspects of Human Cytomegalovirus Diseases

Part of the book series: Frontiers of Virology ((FRVIROLOGY,volume 2))

Summary

Infection of human promyelocytic cells or monocytes with human cytomegalovirus (HCMV) results in transcriptional enhancement of many important inflammatory mediator genes. These include IL-1β, TNF-α, CSF-1, and IL-8/NAP-1. Housekeeping genes and constitutively expressed genes such as lysozyme were not influenced. While IL-1β messenger RNA (mRNA) levels were elevated for at least 4 days postinfection, apparent translational activity was more transient. In situ hybridization techniques were used to demonstrate that a low but significant proportion of monocytes persistently expressed high levels of IL-1β mRNA, similar to that observed immediately after infection. Transfection studies using chloramphenicol acetyltransferase (CAT) constructs of the pro-IL-1β promoter in combination with various HCMV intermediate early (IE) gene region DNA fragments confirmed that the IE region products, particularly region 2, were capable of transactivating inflammatory mediator genes such as IL-1β. Thus a significant proportion of monocytes are persistently modified to express important cytokines that can profoundly modulate systemic immunity.

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References

  1. Anisowicz A, Bardwell L, Sager R (1987) Constitutive over-expression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc Natl Acad Sci USA 84: 7188–7192

    Article  CAS  PubMed  Google Scholar 

  2. Auron PE, Clark BD, Fenton MJ, Rey JL, Webb AC (1989) Regulation of human prointerleukin 1β gene transcription. Colloq INSERM 179: 61–69

    CAS  Google Scholar 

  3. Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 Suppl 97: 77–89

    CAS  Google Scholar 

  4. Brautigam AR, Dutko FJ, Olding LB, Oldstone MBA (1979) Pathogenesis of murine cytomegalovirus infection: the macrophage as a permissive cell for cytomegalovirus infection, replication and latency. J Gen Virol 44: 349–359

    Article  CAS  PubMed  Google Scholar 

  5. Buchmeier NA, Cooper NR (1989) Suppression of monocyte functions by human cytomegalovirus. Immunology 66: 278–283

    CAS  PubMed  Google Scholar 

  6. Carney WP, Hirsch MS (1981) Mechanisms of immunosuppression in CMV mononucleosis. II. Virus—monocyte interactions. J Infect Dis 144: 47–54

    Google Scholar 

  7. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 52945299

    Google Scholar 

  8. Clark BD, Collins KL, Gandy MS, Webb AC, Auron PE (1986) Genomic sequence for human prointerleukin I beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. Nucleic Acids Res 14: 7897–7914

    Article  CAS  PubMed  Google Scholar 

  9. Clouse KA, Robbins PB, Fernie B, Ostrove JM, Fauci AS (1989) Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. J Immunol 143: 470–475

    CAS  PubMed  Google Scholar 

  10. Davis MG, Kenney SC, Kamine J, Pagano JS, Huang E-S (1987) Immediate-early gene region of human cytomegalovirus transactivates the promoter of human immunodeficiency virus. Proc Natl Acad Sci USA 84: 8642–8646

    Article  CAS  PubMed  Google Scholar 

  11. Dinarello CA (1984) Interleukin-1. Rev Infect Dis 6: 51–95

    Article  CAS  Google Scholar 

  12. Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, Figari IS, Palladino Jr MA, O’Connor JV (1986) Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 163: 1433–1450

    Article  CAS  PubMed  Google Scholar 

  13. Dudding LR, Garnett HM (1987) Interaction of strain AD169 and a clinical isolate of cytomegalovirus with peripheral monocytes: the effect of lipopolysaccharide stimulation. J Infect Dis 155: 891–896

    Article  CAS  PubMed  Google Scholar 

  14. Dudding LR, Haskill S, Clark BD, Auron PE, Sporn S, Huang E-S (1989) Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes. J Immunol 143: 3343–3352

    CAS  PubMed  Google Scholar 

  15. Eierman DF, Johnson CE, Haskill JS (1989) Human monocyte inflammatory gene expression is selectively regulated by adherence substrates J Immunol 142: 1970–1976

    CAS  Google Scholar 

  16. Einhorn L, Ost A (1988) Cytomegalovirus infection of human blood cells. J Infect Dis 149: 207–214

    Article  Google Scholar 

  17. Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS (1987) Science 238: 800–802

    Article  CAS  PubMed  Google Scholar 

  18. Gendelman HE, Narayan O, Kennedy-Stoskopf S, Kennedy PFE, Ghotbi Z, Clements JE, Stanley J, Pezeshkpour G (1986) Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol 58: 67–74

    CAS  PubMed  Google Scholar 

  19. Gendelman HE, Orenstein JM, Martin MA, Ferrua C, Mitra R, Phipps T, Wahl LA, Lane HC, Fauci AS, Burke DS, Skillman D, Meltzer MS (1988) Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med 167: 1428–1441

    Article  CAS  PubMed  Google Scholar 

  20. Glisin V, Crkvenjakav R, Byus C (1974) Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry 13: 2633–2637

    Article  CAS  PubMed  Google Scholar 

  21. Gorman CM, Moffat LF, Howard BH (1982) Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 2: 1044–1051

    CAS  PubMed  Google Scholar 

  22. Harris P, Ralph P (1985) Human leukemic models of myelomonocytic development. A review of the HL-60 and U937 cell lines. J Leuk Biol 37: 407–422

    CAS  Google Scholar 

  23. Haskill S, Johnson C, Eierman D, Becker S, Warren K (1988) Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol 140: 1690–1694

    CAS  PubMed  Google Scholar 

  24. Johnson CE (1989) Characterization of inflammatory gene expression in monocytes and in vascular and connective tissue cells. Thesis, University of North Carolina, Chapel Hill

    Google Scholar 

  25. Kapasi K, Rice GPA (1986) The role of the monocyte in cytomegalovirus-mediated immunosuppression in vitro. J Infect Dis 154: 881–884

    Article  CAS  PubMed  Google Scholar 

  26. Kapasi K, Rice GPA (1988) Cytomegalovirus infection of peripheral blood mononuclear cells: effects on interleukin-1 and -2 production and responsiveness. J Virol 62: 36033607

    Google Scholar 

  27. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685

    Article  CAS  PubMed  Google Scholar 

  28. Laimins LA, Gruss P, Pozzatti R, Khoury G (1984) Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol 49:183 — 189

    Google Scholar 

  29. Larsen CG, Anderson AO, Appella E, Oppenheim JJ, Matsushima K (1989) The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science 243: 1464–1466

    Article  CAS  PubMed  Google Scholar 

  30. Nelson JA, Reynolds-Kohler C, Oldstone MBA, Wiley CA (1988) HIV and HCMV coinfect brain cells in patients with AIDS. Virology 165: 286–290

    Article  CAS  PubMed  Google Scholar 

  31. Olafsson K, Smith MS, Marshburn P, Carter S, Haskill S (1991) Variation of HIV infectibility of macrophages as a function of donor, stage of differentiation, and site of origin. J Acquir Immune Defic Syndr 4: 154–164

    CAS  PubMed  Google Scholar 

  32. Petit AJC, Tersmette M, Terpstra FG, de Goede REY, van Lier RAW, Miedema F (1988) Decreased accessory cell function by human monocytic cells after infection with HIV. J Immunol 140: 1485–1489

    CAS  Google Scholar 

  33. Peveri P, Walz A, Dewald B, Baggiolini M (1988) A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med 167: 1547–1559

    Article  CAS  PubMed  Google Scholar 

  34. Renart J, Reiser J, Stark GR (1979) Transfer of proteins from gels to diazobenzyloxymethyl-paper and detection with anti-sera: a method for studying antibody specificity and antigen structure. Proc Natl Acad Sci USA 76: 3116–3120

    Article  CAS  PubMed  Google Scholar 

  35. Rice GPA, Schrier RD, Oldstone MBA (1984) Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc Natl Acad Sci USA 81: 6134–6138

    Article  CAS  PubMed  Google Scholar 

  36. Rodgers GC, Scott DM, Mundin J, Sissons JGP (1985) Monocyto-derived inhibitor or interleukin 1 induced by human cytomegalovirus. J Virol 55: 527–532

    CAS  PubMed  Google Scholar 

  37. Schnittman SM, Psallidopoulos MC, Lane HC, Thompson L, Baseler M, Massari F, Fox CH, Salzman NP, Fauci AS (1989) The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science 245: 305–308

    Article  CAS  PubMed  Google Scholar 

  38. Scott DM, Rodgers BC, Freeke C, Buiter J, Sissons JGP (1989) Human cytomegalovirus and monocytes: limited infection and negligible immunosuppression in normal and mononuclear cells infected in vitro with mycoplasma-free virus strains. J Gen Virol 70: 685–694

    Article  CAS  PubMed  Google Scholar 

  39. Sporn SA, Eierman DF, Johnson DE, Martin G, Ladner M, Haskill S (1990) Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. J Immunol 144: 4434–4441

    CAS  PubMed  Google Scholar 

  40. Wahl SM, Allen JB, Gartner S, Orenstein JM, Popovic M, Chenoweth DE, Arthur LO, Farrar WL, Wahl LM (1989) HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes. J Immunol 142: 3553–3559

    CAS  PubMed  Google Scholar 

  41. Weinshenker BG, Wilson S, Rice GPA (1988) Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol 140:1625 —1631

    Google Scholar 

  42. White BA, Bancroft FC (1982) Cytoplasmic dothybridization: simple analysis of relative RNA levels in multiple small cell or tissue samples. J Biol Chem 257: 8569–8572

    CAS  PubMed  Google Scholar 

  43. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ (1987) Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA 84: 9233–9237

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, Microbiology and Immunology, Medicine, and Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7295, USA

    Stephen Haskill, Lindsay Dudding & Eng-Shang Huang

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  1. Stephen Haskill
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  2. Lindsay Dudding
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  3. Eng-Shang Huang
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Editor information

Editors and Affiliations

  1. Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, POB 1172, 910010, Jerusalem, Israel

    Yechiel Becker

  2. Institut für Medizinische Virologie, Universität Heidelberg, Im Neuenheimer Feld 324, W-6900, Heidelberg, Germany

    Gholamreza Darai

  3. Lineberger Comprehensive Cancer Research Center, The University of North Carolina, CB # 7259, Rm. 117, Lineberger Building, 27599-7295, Chapel Hill, NC, USA

    Eng-Shang Huang Ph. D.

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© 1993 Springer-Verlag Berlin Heidelberg

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Haskill, S., Dudding, L., Huang, ES. (1993). Cytomegalovirus and Macrophage Interaction. In: Becker, Y., Darai, G., Huang, ES. (eds) Molecular Aspects of Human Cytomegalovirus Diseases. Frontiers of Virology, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84850-6_6

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  • DOI: https://doi.org/10.1007/978-3-642-84850-6_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84852-0

  • Online ISBN: 978-3-642-84850-6

  • eBook Packages: Springer Book Archive

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