Archives of Virology

, Volume 98, Issue 1–2, pp 51–64

Human Cytomegalovirus morphogenesis: an ultrastructural study of the late cytoplasmic phases

  • B. Severi
  • M. P. Landini
  • E. Govoni
Original Papers


The late cytoplasmic phases of human Cytomegalovirus (HCMV) morphogenesis in cultured fibroblasts have been studied by transmission electron microscopy focusing attention on the relationship between the viral particles and host cell organelles. The results obtained largely reflect changes in cells subjected to sublethal injurious stimuli induced by many viruses as well as different noxious agents. A great increase in the number of Golgi apparatuses and lysosomes was observed, both of them interacting with the viral progeny. HCMV seems to acquire its final envelope from Golgi-derived structures and, less frequently, from the plasma membrane.


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  1. 1.
    Allison AC, Mallucci L (1965) Histochemical studies of lysosomes and lysosomal enzymes in virus-infected cell cultures. J Exp Med 121: 463–476Google Scholar
  2. 2.
    Arstila AU, Jauregui HO, Chang J, Trump BF (1971) Studies on cellular autophagocytosis. Relationship between heterophagy and autophagy in HeLa cells. Lab Invest 24: 162–174Google Scholar
  3. 3.
    Bainton DF, Farquhar MG (1970) Segregation and packaging of granule enzymes in eosinophilic leucocytes. J Cell Biol 45: 54–73Google Scholar
  4. 4.
    Beker P, Melnick JL, Mayer HD (1965) A morphological comparison between the development stages of Herpes zoster and human cytomegalovirus. Exp Mol Pathol 4: 11–23Google Scholar
  5. 5.
    Cavallo T, Graves K, Cole NL, Albrecht T (1981) Cytomegalovirus: an ultrastructural study of the morphogenesis of nuclear inclusions in human cell culture. J Gen Virol 56: 97–104Google Scholar
  6. 6.
    Cook ML, Stevens JG (1970) Replication of Varicella zoster virus in cell culture: an ultrastructural study. J Ultrastruct Res 32: 334–350Google Scholar
  7. 7.
    Darlington RW, Moss LH (1968) Herpesvirus envelopment. J Virol 2: 48–55Google Scholar
  8. 8.
    de Duve C (1984) A guided tour of the living cell. Scientific American Books, New YorkGoogle Scholar
  9. 9.
    Epstein MA (1962) Observations on the mode of release of Herpesviruses from infected HeLa cells. J Cell Biol 12: 589–597Google Scholar
  10. 10.
    Fedorko ME, Hirsch JG, Cohn ZA (1968) Autophagic vacuoles produced in vitro. J Cell Biol 38: 377–391Google Scholar
  11. 11.
    Fong CKY, Bia F, Hsiung GD, Madore P, Chang PW (1979) Ultrastructural development of guinea pig cytomegalovirus in cultured guinea pig embryo cells. J Gen Virol 42: 127–140Google Scholar
  12. 12.
    Fong CKY, Tenser RB, Hsiung GD, Gross PA (1973) Ultrastructural studies of the envelopment and release of guinea pig herpes-like virus in cultured cells. Virology 52: 488–497Google Scholar
  13. 13.
    Fons MP, Albrecht T (1986) Cytomegalovirus: the relationship of nucleocapsid assembly to the organization of cellulae. Arch Virol 91: 351–356Google Scholar
  14. 14.
    Fons MP, Graves K, Cavallo T, Pollard R, Albrecht T (1986) Human cytomegalovirus: development and progression of nuclear inclusions by primary clinical isolates and laboratory-adapted strains. Proc Soc Exp Biol Med 181: 416–422Google Scholar
  15. 15.
    Gerace L (1985) Traffic control and structural proteins in the eukaryotic nucleus. Nature 318: 508–509Google Scholar
  16. 16.
    Gershon A, Cosio L, Brunell PA (1973) Observations on the growth of Varicella zoster virus in human diploid cells. J Gen Virol 18: 21–31Google Scholar
  17. 17.
    Haguenau F, Michelson-Fiske S (1975) Cytomegalovirus: nucleocapsid assembly and core structure. Intervirology 5: 293–299Google Scholar
  18. 18.
    Hawkins HK (1980) Reactions of lysosomes to cell injury. In: Trump BF, Arstila AV (eds) Pathobiology of cell membranes, vol 2. Academic Press, New York, pp 252–285Google Scholar
  19. 19.
    Hirsimaki P, Arstila AV, Trump BF, Marzella L (1983) Autophagocytosis. In: Trump BF, Arstila AV (eds) Pathobiology of cell membranes, vol 3. Academic Press, New York, pp 201–236Google Scholar
  20. 20.
    Ho M (1982) Pathology of Cytomegalovirus infection. Greenough WR III, Merigan T (eds) Cytomegalovirus biology and infection. Plenum Medical Press, New York, pp 119–212Google Scholar
  21. 21.
    Jasty V, Chang PW (1972) Release of infectious bovine rhinotracheitis virus from productively infected bovine kidney cells: an electron microscopic study. J Ultrastruct Res 38: 433–443Google Scholar
  22. 22.
    Johnson DC, Spear PG (1982) Monensin inhibits the processing of herpes simplex glycoprotiens, their transport to the cell surface and the egress of virions from infected cells. J Virol 43: 1102–1112Google Scholar
  23. 23.
    Johnson DC, Spear PG (1983) O-linked oligosaccharides are required by herpes simplex virus glycoproteins in the Golgi apparatus. Cell 32: 987–997Google Scholar
  24. 24.
    Landini MP, Severi B, Badiali L, Gonczol E, Mirolo G (1987) Structural components of human cytomegalovirus: in situ localization of the major glycoprotein. Intervirology 27: 154–160Google Scholar
  25. 25.
    Landini MP, Severi B, Furlini G, Badiali L (1987) Human cytomegalovirus structural components: intracellular and intraviral localization of p28 and p65–69 by immunoelectron microscopy. Virus Res 8: 15–23Google Scholar
  26. 26.
    Law KM, Wilton Smith P, Farrar GH (1985) A murine monoclonal antibody recognising a single glycoprotein within a human cytomegalovirus virion envelope glycoprotein complex. J Med Virol 17: 255–266Google Scholar
  27. 27.
    Ludwig H (1983) Bovine herpesviruses. In: Roizman B (ed) The Herpesviruses. Plenum Press, New York, pp 135–214Google Scholar
  28. 28.
    Luetzeler J, Heine UI, Wendel E, Prasad U, Ablash DV (1979) Ultrastructural studies on the replication of Herpes Ateles-73 in owl monkey kidney cells. Arch Virol 60: 59–73Google Scholar
  29. 29.
    Maul GD, Rovera G, Vorbrodt A, Abramczuk J (1978) Membrane fusion as a mechanism of SV40 entry into different cellular compartment. J Virol 28: 936–944Google Scholar
  30. 30.
    McAllister RM, Straw RM, Filbert JE, Goodhearth CR (1963) Human cytomegalovirus. Cytochemical observations of intracellular lesion development correlated with viral synthesis and release. Virology 19: 521–531Google Scholar
  31. 31.
    McGavran MH, Smith MG (1965) Ultrastructural, cytochemical and microchemical observations on cytomegalovirus (salivary gland virus) infection of human cells in tissue culture. Exp Mol Pathol 4: 1–10Google Scholar
  32. 32.
    Morgan CH, Rose M, Holden M, Jones EP (1959) Electron microscopic observations on the development of herpes simplex virus. J Exp Med 110: 643–656Google Scholar
  33. 33.
    Morre DJ, Vigil EL (1979) Membrane differentiation within Golgi apparatus of rat hepathocytes. J Ultrastruct Res 68: 317–324Google Scholar
  34. 34.
    Nii S (1971) Electron microscopic observations on FL cells infected with Herpes simples virus. II Envelopment. Biken J 14: 325–348Google Scholar
  35. 35.
    Paine PL, Moore LC, Horowitz SB (1975) Nuclear envelope permeability. Nature 254: 109–114Google Scholar
  36. 36.
    Palade GE (1975) Intracellular aspects of the process of protein synthesis. Science 189: 347–358Google Scholar
  37. 37.
    Papadimitriou JM, Shellam GR, Robertson TA (1984) An ultrastructural investigation of cytomegalovirus replication in murine hepatocytes. J Gen Virol 65: 1979–1990Google Scholar
  38. 38.
    Patrizi G, Middelkamp JN, Reed CA (1967) Reduplication of nuclear membranes in tissue culture cells infected with guinea pig cytomegalovirus. Am J Pathol 50: 779–790Google Scholar
  39. 39.
    Porter KR (1961) The ground substance: observations from electron microscopy. In: Brachet J, Mirsky AE (eds) The cell, vol 2. Academic Press, New York, pp 621–672Google Scholar
  40. 40.
    Rowe WP, Hartley JW, Waterman S, Turner HC, Huebner RJ (1965) Cytopathogenic agent resembling human salivary gland virus recovered from tissue cultures of human adenoid. Proc Soc Exp Biol Med 92: 418–424Google Scholar
  41. 41.
    Ruebner BH, Hirano T, Slusser RJ, Medearis DN (1965) Human cytomegalovirus infection: electron microscopic and histochemical changes in cultures of human fibroblasts. Am J Pathol 46: 477–499Google Scholar
  42. 42.
    Ruebner BH, Miyai K, Slusser RJ, Wedemyer P, Medearis DN Jr (1964) Mouse cytomegalovirus infection. An electron microscopic study of hepatic parenchymal cells. Am J Pathol 44: 799–821Google Scholar
  43. 43.
    Schwartz J, Roizman B (1969) Concerning the egress of herpes simplex virus from infected cells: electron and light microscopic observations. Virology 38: 42–49Google Scholar
  44. 44.
    Schwartz J, Roizman B (1969) Similarities and differences in the development of laboratory strains and freshly isolated strains of Herpes simplex Virus in Hep-2 cells: electron microscopy. J Virol 4: 879–889Google Scholar
  45. 45.
    Severi B, Landini MP, Musiani M, Zerbini M (1979) A study of the passage of human cytomegalovirus from the nucleus to the cytoplasm. Microbiologica 2: 265–273Google Scholar
  46. 46.
    Siminoff P, Menefee MG (1966) Normal and 5-bromodeoxyuridine inhibited development of herpes simplex virus: an electron microscope study. Exp Cell Res 44: 241–255Google Scholar
  47. 47.
    Smith JD (1980) An additional role for the outer nuclear membrane in the morphogenesis of Herpes simplex virus. Intervirology 13: 312–316Google Scholar
  48. 48.
    Smith JD, De Harven E (1973) Herpes simplex virus and human cytomegalovirus replication in WI38 cells. I. Sequence of viral replication. J Virol 12: 919–930Google Scholar
  49. 49.
    Smith JD, De Harven E (1978) Herpes simplex virus and cytomegalovirus replication in WI38 cells. III. Cytochemical localization of lysosomal enzymes in infected cells. J Virol 26: 102–109Google Scholar
  50. 50.
    Smith MG (1956) Propagation in tissue cultures of a cytopathogenic virus from human salivary gland virus disease. Proc Soc Exp Biol Med 92: 424–430Google Scholar
  51. 51.
    Stackpole CW (1969) Herpes-type virus of the frog renal adenocarcinoma. I. Virus development in tumor transplants maintained at low temperature. J Virol 4: 75–93Google Scholar
  52. 52.
    Stinski MF (1976) Human Cytomegalovirus: glycoproteins associated with virions and dense bodies. J Virol 19: 594–605Google Scholar
  53. 53.
    Strandberg JD, Aurelian L (1969) Replication of canine Herpesvirus. II. Virus development and release in infected dog kidney cells. J Virol 4: 480–489Google Scholar
  54. 54.
    Tamm I (1975) Cell injury with viruses. Am J Pathol 81: 163–178Google Scholar
  55. 55.
    Trump BF, Arstila AU (1975) Cell membranes and diseases processes. In: Trump BF, Arstila AU (eds) Pathobiology of cell membranes, vol 1. Academic Press, New York, pp 1–103Google Scholar
  56. 56.
    Weiland F, Keil GM, Reddehase MJ, Koszinowski UK (1986) Studies on the morphogenesis of murine cytomegalovirus. Intervirology 26: 192–201Google Scholar
  57. 57.
    Weller TH, Macauley JC, Craig JM, Wirth P (1957) Isolation of intranuclear inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease. Proc Soc Exp Biol Med 94: 4–12Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • B. Severi
    • 1
  • M. P. Landini
    • 2
  • E. Govoni
    • 1
  1. 1.Institute of Clinical Electron MicroscopyUniversity of BolognaBolognaItaly
  2. 2.Institute of MicrobiologyUniversity of BolognaBolognaItaly

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