Advertisement

Archives of oto-rhino-laryngology

, Volume 232, Issue 2, pp 165–177 | Cite as

Coronavirus-associated antibodies in nasopharyngeal carcinoma and infectious mononucleosis

  • W. Arnold
  • M. Klein
  • J. B. Wang
  • W. A. K. Schmidt
  • H. J. Trampisch
Article

Summary

Coronavirus-like particles are found within the cytoplasm of NPC tumor cells, within the cytoplasm of the tumor cells of the regional metastases, and within tumor cells grown on nude mice. For the immunologic identification of the coronaviruses, the cultures of human tracheal epithelium (MRC-C) were used and inoculated with a known coronavirus strain. Whereas blood sera from NPC patients (n=73) contain significantly elevated antibody titers against corona viruses, unselected sera from patients without NPC showed a low antibody titer (n=83). Only patients suffering from infectious mononucleosis (n=40) showed a titer pattern similar to that of NPC patients. For demonstration of antigen-antibody reaction within the NPC tumor cell cytoplasm, sera with a high antibody content against coronaviruses deriving from other than NPC patients or anticoronavirus sera from rabbits were used. By indirect immunofluorescence, the NPC tumor cells showed a bright cytoplasmic fluorescence. No fluorescence was seen when tumor cells were exposed to human sera with known low or absent corona antibody titer or to normal rabbit sera. The results indicate that next to a DNA virus infection (EBV), an RNA virus infection (coronavirus) may play a role in NPC as well as in infectious mononucleosis.

Key words

Coronavirus-specific antibodies in sera of NPC and infectious mononucleosis patients Positive immunofluorescent reaction to corona-viruses within the cytoplasm of NPC tumor cells Statistical analysis 

Antikörper gegen Coronaviren beim Nasopharynxkarzinom und bei der infektiösen Mononukleose

Zusammenfassung

Coronavirusähnliche cytoplasmatische Einschlüsse waren in Tumorzellen des Nasopharynxkarzinoms, seiner Metastase und nach Transplantation auf die nackte Maus elektronenoptisch gefunden worden. Zur immunofluoreszenzmikroskopischen Darstellung der Coronaviren wurden Zellkulturen aus menschlichen Trachealepithelien benutzt, die mit einem bekannten Stamm von Coronaviren infiziert wurden. Die infizierten Zellkulturen dienten als bekanntes Antigen, an dem mittels des indirekten Immunfluoreszenztestes 83 Kontrollseren, 73 Seren von NPC-Patienten und 40 Seren von Patienten mit gesicherter Mononucleose ausgetestet wurden. Es ließ sich eindeutig nachweisen, daß Patienten mit NPC oder IM einen signifikant höheren Antikörpertiter im Serum besitzen als gesunde Vergleichspersonen oder Patienten mit anderen Erkrankungen. Ferner benützten wir vom Kaninchen stammende Anti-Corona-Antikörper, um an der Tumorzelle des NPC die ausschließliche cytoplasmatische Lokalisation des Antigens nachzuweisen. Während beim EBNA-Test zum Nachweis der kerngebundenen Epstein-Barr-Antigene ausschließlich die Tumorzellkerne fluoreszieren, leuchten in den Tupfpräparaten des gleichen Tumormaterials beim Coronatest nur die cytoplasmatischen Zellanteile. Die Untersuchungen deuten an, daß beim Nasopharynxkarzinom und bei der infektiösen Mononucleose neben der bekannten Epstein-Barr-Virusinfektion (DNS-Viren) auch eine RNS-Virusinfektion (Coronaviren) eine Rolle spielen können.

Schlüsselwörter

Coronavirusspezifische Antikörper im Serum von NPC-Kranken und bei Mononukleose Positive Immunofluoreszenz auf Coronaviren im Cytoplasma von NPC-Tumorzellen Statistische Auswertung 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Achong BG, Mansell PW, Epstein MA (1971) An unusual virus in cultures from a human nasopharyngeal carcinoma. J Natl Cancer Inst 46:299–307Google Scholar
  2. Andersson-Anvret M, Forsby N, Klein G, Henle W (1977) Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histophathological examination. Int J Cancer 20:486–494Google Scholar
  3. Arnold W, Huth F (1979a) Viren, virusähnliche und auf Viren hinweisende Strukturen beim Karzinom des Nasopharynx. Arch Otorhinolaryngol (NY) 222:295–317Google Scholar
  4. Arnold W, Huth F (1979b) Light- and electron-microscopic investigations of nasopharyngeal carcinomas with regard to the viral etiology of these tumors. J Cancer Res Clin Oncol 94:87–109Google Scholar
  5. Arnold W, Huth F, Lindenberger J, Vosteen KH (1980a) Vergleichende Morphologie des lymphoepithelialen Karzinoms: Primärtumor-Metastase-Xenotransplantat. Arch Otorhinolaryngol (NY) 226:15–26Google Scholar
  6. Arnold W, Huth F (1980b) Morphological and immunohistochemical investigations of human NPC before and after transplantation to nude mice. XII. Internat Symp NPC, Oct 23–25, DüsseldorfGoogle Scholar
  7. Arnold W, Nakazima A, Wang JB, Vosteen KH, Brunner H, Goebel U (1980c) Aktuelle Aspekte zur Ätiologie, Diagnostik und Therapie des Nasenrachenraumkarzinoms (NPC). HNO 28:247–260Google Scholar
  8. Bridger JC, Caul EO, Egglestone SI (1978) Replication of an enteric bovine Coronavirus in intestinal organ cultures. Arch Virol 57:43–51Google Scholar
  9. Burks JS, DeVald BL, Jankovsky LD, Gerdes JC (1980) Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients. Science 209:933–934Google Scholar
  10. Cartwright SF, Lucas M (1970) Vomiting and wasting disease of piglets. Vet Rec 86:278–280Google Scholar
  11. DeSchryver A, Klein G, Henle G, Henle W, Cameron HM, Santesson L, Clifford P (1972) EB-virus associated serology in malignant disease: antibody levels to viral capsid antigens (VCA), membrane antigens (MA) and early antigens (EA) in patients with various neoplastic conditions. Int J Cancer 9:353–364Google Scholar
  12. Epstein MA, Achong BG, Ball G (1974) Further observations on a human syncytial virus from a nasopharyngeal carcinoma. J Natl Cancer Inst 53:681–688Google Scholar
  13. Graffi A, Schramm T, Bender E, Graffi I, Horn KH, Bierwolf D (1968) Cell-free transmissible leukoses in syrian hamsters, probably of viral etiology. Br J Cancer 22:577–581Google Scholar
  14. Graffi A, Bender E, Schramm T, Kuhn W, Schneiders F (1969) Induction of transmissible lymphomas in Syrian hamsters by application of DNA from viral hamster Papovavirus-induced tumors and by cell-free filtrates from human tumors. Proc Natl Acad Sci USA 64:1172–1175Google Scholar
  15. Graffi A, Bender E, Schramm T, Graffi I, Niezabitowski A, Schneiders F (1976) Durch ein Oncornavirus induzierte, zellfrei übertragbare Sarkome des Goldhamsters. Arch Geschwulstforsch 46:77–84Google Scholar
  16. Graffi A (1979) Zur Ätiologie der Geschwülste. Med Uns Zeit 4:123–131Google Scholar
  17. Henle W, Henle G, Lennette ET (1979) The Epstein-Barr virus. Sci Am 241:40–51Google Scholar
  18. Herndon RM, Griffin DE, McCormick U, Weiner LP (1975) Mouse hepatitis virus-induced recurrent demyelination. Arch Neurol 32:32–35Google Scholar
  19. Hsu MM, Chiou JF, McCabe BF (1974) Anti-Epstein-Barr virus antibody in nasopharyngeal carcinoma. Ann Otol 83:19–25Google Scholar
  20. Lenoir G, DeThé G (1978) Epstein-Barr virus — epithelial cell interaction and its implication in the etiology of nasopharyngeal carcinoma. In: DeThé G, Ito Y (eds) Nasopharyngeal Carcinoma: Etiology and control. IARC, Lyon, pp 377–384Google Scholar
  21. Mai K (1959) Vorteile eines Rinderblutzellen-Lysin-Testes in der Diagnostik der infektiösen Mononukleose. Zentrabl Bakteriol 176:367–370Google Scholar
  22. McIntosh K, Kapikian AZ, Hardison KH, Hartley JW, Chanock RM (1969) Antigenic relationship among the corona-viruses of man and between human and animal coronaviruses. J Immunol 102:1109–1118Google Scholar
  23. McIntosh K, Kapikian AZ, Turner HC, Hartley JW, Parrott RH, Chanock RM (1970) Seroepidemiologic studies of Coronavirus infection in adults and children. Am J Epidemiol 91:585–592Google Scholar
  24. McIntosh K (1974) Coronaviruses: A comparative review. Curr Top Microbiol Immunol 63:85–129Google Scholar
  25. Morgan DG, Miller G, Niederman IC, Smith HW, Dowaliby IM (1979) Sites of Epstein-Barr virus replication in the oropharynx. Lancet 2:1154–1157Google Scholar
  26. Moses HL, Glade PR, Kasel JA, Rosenthal AS, Hirshaut Y, Chessin LN (1968) Infectious mononucleosis: Detection of herpes-like virus and reticular aggregates of small cytoplasmatic particles in continous lymphoid cell lines derived from peripheral blood. Proc Natl Acad Sci USA 60:489–496Google Scholar
  27. Oshiro LS (1973) Coronaviruses. In: Dalton AJ, Haguenau F (eds) Ultrastructure of animal viruses and bacteriophages. Academic Press, New York London, pp 331–343Google Scholar
  28. Prasad U, Gogusev J (1978) Intracisternal tubular inclusions in nasopharyngeal carcinoma. J Laryngol Otol 92:979–989Google Scholar
  29. Tanaka R, Iwasaki Y, Koprowski H (1976) Intracisternal virus-like particles in brain of a multiple sclerosis patient. J Neurol Sci 28:121–126Google Scholar
  30. Tyrrell DAJ, Bynoe ML, Hoorn B (1968) Cultivation of difficult viruses from patient with common colds. Br Med J 1:606–610Google Scholar
  31. Tyrrell DAJ, Almeida JD, Cunningham CH, Dowdle WR, Hofstad MS, McIntosh K, Tajima M, Zakstelskaja LY, Easterday BC, Kapikian A, Bingham RW (1975) Coronaviridae. Intervirology 5:76–82Google Scholar
  32. Tyrrell DAJ, Alexander DJ, Almeida JD, Cunningham CH, Easterday BC, Garwes DJ, Hierholzer JC, Kapikian A, MacNaughton MR, McIntosh K (1978) Coronaviridae: Second report. Intervirology 10:321–328Google Scholar
  33. Wolf H, Wilmes E (1980) Evidence for the presence of EB-viruses in the parotid gland. Abstr. Herpes Viruses, Cold Spring Harbor, Aug. 1980Google Scholar
  34. Wyatt RG, Kapikian AZ, Thornhill TS, Sereno MM, Kim HW, Chanock RM (1974) In vitro cultivation in human foetal intestinal organ culture of a reovirus-like agent associated with non-bacterial gastroenteritis in infants and children. J Infect Dis 130:523–528Google Scholar
  35. Zur Hausen H (1976) Biochemical approaches to detection of Epstein-Barr virus in human tumors. Cancer Res 36:678–680Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • W. Arnold
    • 1
  • M. Klein
    • 2
  • J. B. Wang
    • 1
  • W. A. K. Schmidt
    • 2
  • H. J. Trampisch
    • 3
  1. 1.Dept. of OtorhinolaryngologyUniversity of DüsseldorfDüsseldorf 1Federal Republic of Germany
  2. 2.Institute for Medical Microbiology and VirologyUniversity of DüsseldorfDüsseldorf 1Federal Republic of Germany
  3. 3.Institute for Medical Statistics and BiomathematicsUniversity of DüsseldorfDüsseldorf 1Federal Republic of Germany

Personalised recommendations