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. 1955 Jun 1;101(6):577–590. doi: 10.1084/jem.101.6.577

ELECTRON MICROSCOPY OF EARLY CYTOPLASMIC CHANGES DUE TO INFLUENZA VIRUS

Carl G Harford 1, Alice Hamlin 1, Esther Parker 1
PMCID: PMC2136481  PMID: 14367680

Abstract

Recently improved methods for visualization of thin tissue sections by electron microscopy have been applied to the study of early changes in the bronchial epithelium of mice infected by inhalation of aerosols of influenza virus. In confirmation of previous findings by the authors, inclusion bodies have been demonstrated in ciliated and non-ciliated cells of infected bronchial epithelium. In addition to 3 strains of mouse-adapted Type A virus, 2 unadapted strains gave qualitatively the same results. The inclusion bodies were found to be composed largely of particles of a size estimated to correspond to the known size of influenza virus. The viral lesion of the cytoplasm was also associated with linear formations which were thought to be abnormal forms of endoplasmic reticulum. Well developed microvilli were found on the ciliated borders of ciliated cells, but no evidence was found of viral growth in this region.

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Selected References

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  1. BANG F. B. Cellular changes in the chick chorio-allantoic membrane infected with herpes simplex and vaccinia; a study with thin sections for the electron microscope. Bull Johns Hopkins Hosp. 1950 Dec;87(6):511–547. [PubMed] [Google Scholar]
  2. BORYSKO E., BANG F. B. The fine structure of the chorio-allantoic membrane of the normal chick embryo. Bull Johns Hopkins Hosp. 1953 Apr;92(4):257–289. [PubMed] [Google Scholar]
  3. BOYD J. D., HUGHES A. F. Observations on human chorionic villi using the electron microscope. J Anat. 1954 Jul;88(3):356–362. [PMC free article] [PubMed] [Google Scholar]
  4. CHU C. M., DAWSON I. M., ELFORD W. J. Filamentous forms associated with newly isolated influenza virus. Lancet. 1949 Apr 9;1(6554):602–602. doi: 10.1016/s0140-6736(49)91699-2. [DOI] [PubMed] [Google Scholar]
  5. COFFIN D. L., COONS A. H., CABASSO V. J. A histological study of infectious canine hepatitis by means of fluorescent antibody. J Exp Med. 1953 Jul;98(1):13–20. doi: 10.1084/jem.98.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DALTON A. J. Electron micrography of epithelial cells of the gastro-intestinal tract and pancreas. Am J Anat. 1951 Jul;89(1):109–133. doi: 10.1002/aja.1000890105. [DOI] [PubMed] [Google Scholar]
  7. DAWSON I. M., ELFORD W. J. The investigation of influenza and related viruses in the electron microscope, by a new technique. J Gen Microbiol. 1949 May;3(2):298–311. doi: 10.1099/00221287-3-2-298. [DOI] [PubMed] [Google Scholar]
  8. DE MARS R. I., LURIA S. E., FISHER H., LEVINTHAL C. The production of incomplete bacteriophage particles by the action of proflavine and the properties of the incomplete particles. Ann Inst Pasteur (Paris) 1953 Jan;84(1):113–128. [PubMed] [Google Scholar]
  9. DEMPSEY E. W. Electron microscopy of the visceral yolk-sac epithelium of the guinea pig. Am J Anat. 1953 Nov;93(3):331–363. doi: 10.1002/aja.1000930303. [DOI] [PubMed] [Google Scholar]
  10. DEMPSEY E. W., LANSING A. I. Improved knife-holders for thin-sectioning with rotary microtomes. Proc Soc Exp Biol Med. 1953 Feb;82(2):253–256. doi: 10.3181/00379727-82-20082. [DOI] [PubMed] [Google Scholar]
  11. DONALD H. B., ISAACS A. Some properties of influenza virus filaments shown by electron microscopic particle counts. J Gen Microbiol. 1954 Oct;11(2):325–331. doi: 10.1099/00221287-11-2-325. [DOI] [PubMed] [Google Scholar]
  12. EDDY B. E., WYCKOFF R. W. G. Influenza virus in sectioned tissues. Proc Soc Exp Biol Med. 1950 Oct;75(1):290–293. doi: 10.3181/00379727-75-18174. [DOI] [PubMed] [Google Scholar]
  13. EPSTEIN B., REISSIG M., DE ROBERTIS E. Studies by electron microscopy of thin sections of infectious myxomatosis in rabbits. J Exp Med. 1952 May;95(5):347–354. doi: 10.1084/jem.96.4.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Firor W. M., Gey G. O. The Study of Malignant Cells with Phase Difference Microscopy. Ann Surg. 1947 May;125(5):604–605. [PMC free article] [PubMed] [Google Scholar]
  15. Friedewald W. F., Pickels E. G. CENTRIFUGATION AND ULTRAFILTRATION STUDIES ON ALLANTOIC FLUID PREPARATIONS OF INFLUENZA VIRUS. J Exp Med. 1944 Mar 1;79(3):301–317. doi: 10.1084/jem.79.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. GAYLORD W. H., Jr, MELNICK J. L., BUNTING H. Intracellular development of vaccinia virus. Proc Soc Exp Biol Med. 1952 May;80(1):24–27. doi: 10.3181/00379727-80-19509. [DOI] [PubMed] [Google Scholar]
  17. GAYLORD W. H., Jr, MELNICK J. L. Intracellular forms of pox viruses as shown by the electron microscope (Vaccinia, Ectromelia, Molluscum Contagiosum). J Exp Med. 1953 Aug;98(2):157–172. doi: 10.1084/jem.98.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. GRAY A., SCOTT T. F. M. Some observations on the intracellular localization of the virus of herpes simplex in the chick embryo liver. J Exp Med. 1954 Nov 1;100(5):473–484. doi: 10.1084/jem.100.5.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. HARFORD C. G., HAMLIN A. Effect of influenza virus on cilia and epithelial cells in the bronchi of mice. J Exp Med. 1952 Feb;95(2):173–190. doi: 10.1084/jem.95.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. HOTTLE G. A., MORGAN C., PEERS J. H., WYCKOFF R. W. G. The electron microscopy of rabies inclusion (Negri) bodies. Proc Soc Exp Biol Med. 1951 Aug;77(4):721–723. doi: 10.3181/00379727-77-18905. [DOI] [PubMed] [Google Scholar]
  21. HOUCK C. E., DEMPSEY E. W. Cytological staining procedures applicable to methacrylate-embedded tissues. Stain Technol. 1954 Jul;29(4):207–211. doi: 10.3109/10520295409115470. [DOI] [PubMed] [Google Scholar]
  22. Harford C. G., Smith M. R., Wood W. B. SULFONAMIDE CHEMOTHERAPY OF COMBINED INFECTION WITH INFLUENZA VIRUS AND BACTERIA. J Exp Med. 1946 May 31;83(6):505–518. [PMC free article] [PubMed] [Google Scholar]
  23. Heinmets F. Studies with the Electron Microscope on the Interaction of Red Cells and Influenza Virus. J Bacteriol. 1948 Jun;55(6):823–831. doi: 10.1128/jb.55.6.823-831.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hirst G. K. STUDIES ON THE MECHANISM OF ADAPTATION OF INFLUENZA VIRUS TO MICE. J Exp Med. 1947 Oct 31;86(5):357–366. doi: 10.1084/jem.86.5.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. LATTA H., HARTMANN J. F. Use of a glass edge in thin sectioning for electron microscopy. Proc Soc Exp Biol Med. 1950 Jun;74(2):436–439. doi: 10.3181/00379727-74-17931. [DOI] [PubMed] [Google Scholar]
  26. LEVINTHAL C., FISHER H. The structural development of a bacterial virus. Biochim Biophys Acta. 1952 Oct;9(4):419–429. doi: 10.1016/0006-3002(52)90187-x. [DOI] [PubMed] [Google Scholar]
  27. Lauffer M. A., Stanley W. M. BIOPHYSICAL PROPERTIES OF PREPARATIONS OF PR8 INFLUENZA VIRUS. J Exp Med. 1944 Dec 1;80(6):531–548. doi: 10.1084/jem.80.6.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. MORGAN C., ELLISON S. A., ROSE H. M., MOORE D. H. Electron microscopic examination of inclusion bodies of herpes simplex virus. Proc Soc Exp Biol Med. 1953 Mar;82(3):454–457. [PubMed] [Google Scholar]
  29. MORGAN C., ELLISON S. A., ROSE H. M., MOORE D. H. Structure and development of viruses as observed in the electron microscope. I. Herpes simplex virus. J Exp Med. 1954 Aug 1;100(2):195–202. doi: 10.1084/jem.100.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. MORGAN C., ELLISON S. A., ROSE H. M., MOORE D. H. Structure and development of viruses observed in the electron microscope. II. Vaccinia and fowl pox viruses. J Exp Med. 1954 Sep 1;100(3):301–310. doi: 10.1084/jem.100.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. MORGAN C., WYCKOFF R. W. G. The electron microscopy of fowl pox virus within the chorioallantoic membrane. J Immunol. 1950 Aug;65(2):285–295. [PubMed] [Google Scholar]
  32. MOULTON J. E., BROWN C. H. Antigenicity of canine distemper inclusion bodies as demonstrated by fluorescent antibody technic. Proc Soc Exp Biol Med. 1954 May;86(1):99–102. doi: 10.3181/00379727-86-21021. [DOI] [PubMed] [Google Scholar]
  33. MURPHY J. S., BANG F. B. Observations with the electron microscope on cells of the chick chorio-allantoic membrane infected with influenza virus. J Exp Med. 1952 Mar;95(3):259–268. doi: 10.1084/jem.95.3.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. MURPHY J. S., KARZON D. T., BANG F. B. Studies of influenza A (pr8) infected tissue cultures by electron microscopy. Proc Soc Exp Biol Med. 1950 Apr;73(4):596–599. doi: 10.3181/00379727-73-17756. [DOI] [PubMed] [Google Scholar]
  35. Newman S. B., Borysko E., Swerdlow M. New Sectioning Techniques for Light and Electron Microscopy. Science. 1949 Jul 15;110(2846):66–68. doi: 10.1126/science.110.2846.66. [DOI] [PubMed] [Google Scholar]
  36. Olitsky P. K., Harford C. G. Intranuclear Inclusion Bodies in the Tissue Reactions Produced by Injections of Certain Foreign Substances. Am J Pathol. 1937 Sep;13(5):729–748.3. [PMC free article] [PubMed] [Google Scholar]
  37. PALADE G. E. A study of fixation for electron microscopy. J Exp Med. 1952 Mar;95(3):285–298. doi: 10.1084/jem.95.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. PALADE G. E., PORTER K. R. Studies on the endoplasmic reticulum. I. Its identification in cells in situ. J Exp Med. 1954 Dec 1;100(6):641–656. doi: 10.1084/jem.100.6.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. PALADE G. E. The fine structure of mitochondria. Anat Rec. 1952 Nov;114(3):427–451. doi: 10.1002/ar.1091140304. [DOI] [PubMed] [Google Scholar]
  40. PORTER K. R., BLUM J. A study in microtomy for electron microscopy. Anat Rec. 1953 Dec;117(4):685–710. doi: 10.1002/ar.1091170403. [DOI] [PubMed] [Google Scholar]
  41. PORTER K. R. Electron microscopy of basophilic components of cytoplasm. J Histochem Cytochem. 1954 Sep;2(5):346–375. doi: 10.1177/2.5.346. [DOI] [PubMed] [Google Scholar]
  42. PORTER K. R. Observations on a submicroscopic basophilic component of cytoplasm. J Exp Med. 1953 May;97(5):727–750. doi: 10.1084/jem.97.5.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. REAGAN R. L., BRUECKNER A. L. Electron micrographs of Negri bodies found in rabies. J Infect Dis. 1950 Nov-Dec;87(3):213–216. doi: 10.1093/infdis/87.3.213. [DOI] [PubMed] [Google Scholar]
  44. WANG C. I. The relation of infectious and hemagglutination titers to the adaptation of influenza virus to mice. J Exp Med. 1948 Nov;88(5):515–519. doi: 10.1084/jem.88.5.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. WATSON B. K., COONS A. H. Studies of influenza virus infection in the chick embryo using fluorescent antibody. J Exp Med. 1954 May 1;99(5):419–428. doi: 10.1084/jem.99.5.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. WEISS J. M. The ergastoplasm; its fine structure and relation to protein synthesis as studied with the electron microscope in the pancreas of the Swiss albino mouse. J Exp Med. 1953 Dec;98(6):607–618. doi: 10.1084/jem.98.6.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. WYCKOFF R. W. G. Electron microscopy of chick embryo membrane infected with PR-8 influenza. Nature. 1951 Oct 13;168(4276):651–652. doi: 10.1038/168651a0. [DOI] [PubMed] [Google Scholar]
  48. Woodruff C. E., Goodpasture E. W. The Infectivity of Isolated Inclusion Bodies of Fowl-Pox. Am J Pathol. 1929 Jan;5(1):1–10.7. [PMC free article] [PubMed] [Google Scholar]
  49. Woodruff C. E., Goodpasture E. W. The Relation of the Virus of Fowl-Pox to the Specific Cellular Inclusions of the Disease. Am J Pathol. 1930 Nov;6(6):713–720.3. [PMC free article] [PubMed] [Google Scholar]

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