Advertisement

Journal of NeuroVirology

, Volume 12, Issue 2, pp 90–99 | Cite as

Lack of association of herpesviruses with brain tumors

  • S. Poltermann
  • B. Schlehofer
  • K. Steindorf
  • P. Schnitzler
  • K. Geletneky
  • J. R. Schlehofer
Article

Abstract

Gliomas are the most frequent primary brain tumors in humans. Many studies have been carried out on their etiology; however, the only confirmed risk factors are hereditary predisposing conditions and high dose of ionizing radiation. Recently, human cytomegalovirus (HCMV) gene products and nucleic acids were reported to be present in all of 27 glioma samples investigated in contrast to other brain tissues, and it was hypothesized that HCMV might play a role in glioma pathogenesis. To evaluate these findings, samples of 40 gliomas, 31 meningiomas, and 6 acoustic neurinomas (ACNs) were analyzed for the presence of HCMV macromolecules using polymerase chain reaction (PCR) and immunohistochemistry. Additionally, corresponding blood samples from 72 patients were analyzed for the presence of HCMV DNA to check for a possible contamination of tumor tissues with HCMV-infected blood cells. No HCMV DNA sequences were found, neither in brain tumor tissues nor in corresponding blood samples. Immunohistochemistry did not detect HCMV-specific proteins. Addressing a possible role of other herpesviruses as has been suggested in seroepidemiological studies, seroprevalences of antibodies to HCMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) were determined by enzyme-linked immunosorbent assay (ELISA). Serological analyses of brain tumor patients showed no significant differences in the prevalences of antibodies to HCMV, HSV, EBV, or VZV compared to the general population. Thus, the data of the present study do not support the hypothesis of an association of herpesviruses with the development of primary brain tumors.

Keywords

Epstein-Barr virus herpes simplex virus human cytomegalovirus varicella-zoster virus 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Becker N (1998). Atlas of cancer mortality in the Federal Republic of Germany. Berlin, Heidelberg: Springer.Google Scholar
  2. Bondy ML, Wrensch MR (1996). Epidemiology of primary malignant brain tumours. Baillieres Clin Neurol 5: 251–270.PubMedGoogle Scholar
  3. Britt W, Alford C (1996). Cytomegalovirus. In: Fields virology. Fields B, Knipe D, Howley P (eds). Philadelphia: Lippincott-Raven Publishers, pp 2493–2523.Google Scholar
  4. Castillo JP, Kowalik TF (2002). Human cytomegalovirus immediate early proteins and cell growth control. Gene 290: 19–34.PubMedCrossRefGoogle Scholar
  5. Castillo JP, Yurochko AD, Kowalik TF (2000). Role of human cytomegalovirus immediate-early proteins in cell growth control. J Virol 74: 8028–8037.PubMedCrossRefGoogle Scholar
  6. Chee M, Rudolph SA, Plachter B, Barrell B, Jahn G (1989). Identification of the major capsid protein gene of human cytomegalovirus. J Virol 63: 1345–1353.PubMedGoogle Scholar
  7. Cinatl J, Jr, Scholz M, Doerr HW (2005). Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulation. Med Res Rev 25: 167–185.PubMedCrossRefGoogle Scholar
  8. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, Nabors LB, Cobbs CG, Britt WJ (2002). Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res 62: 3347–3350.PubMedGoogle Scholar
  9. Cohen JI (2000). Epstein-Barr virus infection. N Engl J Med 343: 481–492.PubMedCrossRefGoogle Scholar
  10. Doniger J, Muralidhar S, Rosenthal LJ (1999). Human cytomegalovirus and human herpesvirus 6 genes that transform and transactivate. Clin Microbiol Rev 12: 367–382.PubMedGoogle Scholar
  11. Fritschy JM, Brandner S, Aguzzi A, Koedood M, Luscher B, Mitchell PJ (1996). Brain cell type specificity and gliosis-induced activation of the human cytomegalovirus immediate-early promoter in transgenic mice. J Neurosci 16: 2275–2282.PubMedGoogle Scholar
  12. Gass P, Kiessling M, Schafer P, Mester C, Schmitt HP, Kuhn JE (1993). Detection of human cytomegalovirus DNA in paraffin sections of human brain by polymerase chain reaction and the occurrence of false negative results. J Neurol Neurosurg Psychiatry 56: 211–214.PubMedCrossRefGoogle Scholar
  13. Hadfield MG, Murray BK, Thomson TA, Young HF (1984). Herpesvirus type 1 serum antibodies and brain tumors in humans. Clin Neuropathol 3: 68–71.PubMedGoogle Scholar
  14. Harkins L, Volk AL, Samanta M, Mikolaenko I, Britt WJ, Bland KI, Cobbs CS (2002). Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet 360: 1557–1563.PubMedCrossRefGoogle Scholar
  15. Hellenbrand W, Thierfelder W, Muller-Pebody B, Hamouda O, Breuer T (2005). Seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in former East and West Germany, 1997–1998. Eur J Clin Microbiol Infect Dis 24: 131–135.PubMedCrossRefGoogle Scholar
  16. Herrero YC, Cornelis JJ, Herold-Mende C, Rommelaere J, Schlehofer JR, Geletneky K (2004). Parvovirus H-1 infection of human glioma cells leads to complete viral replication and efficient cell killing. Int J Cancer 109: 76–84.CrossRefGoogle Scholar
  17. Ho M (1990). Epidemiology of cytomegalovirus infections. Rev Infect Dis 12 (Suppl 7): S701-S710.PubMedCrossRefGoogle Scholar
  18. Huang G, Yan Q, Wang Z, Chen X, Zhang X, Guo Y, Li JJ (2002). Human cytomegalovirus in neoplastic cells of Epstein-Barr virus negative Hodgkin’s disease. Int J Oncol 21: 31–36.PubMedGoogle Scholar
  19. Inskip PD, Linet MS, Heineman EF (1995). Etiology of brain tumors in adults. Epidemiol Rev 17: 382–414.PubMedGoogle Scholar
  20. Knosel T, Schewe C, Dietel M, Petersen I (2004). Cytomegalovirus is not associated with progression and metastasis of colorectal cancer. Cancer Lett 211: 243–247.PubMedCrossRefGoogle Scholar
  21. Krech U (1973). Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ 49: 103–106.PubMedGoogle Scholar
  22. Landolfo S, Gariglio M, Gribaudo G, Lembo D (2003). The human cytomegalovirus. Pharmacol Ther 98: 269–297.PubMedCrossRefGoogle Scholar
  23. Lau SK, Chen YY, Chen WG, Diamond DJ, Mamelak AN, Zaia JA, Weiss LM (2005). Lack of association of cytomegalovirus with human brain tumors. Mod Pathol 18: 838–843.PubMedCrossRefGoogle Scholar
  24. Lokensgard JR, Cheeran MC, Gekker G, Hu S, Chao CC, Peterson PK (1999). Human cytomegalovirus replication and modulation of apoptosis in astrocytes. J Hum Virol 2: 91–101.PubMedGoogle Scholar
  25. Mangano M, Hodinka R, Spivack J (1992). Detection of human cytomegalovirus by polymerase chain reaction. In: Diagnosis of human viruses by polymerase chain reaction technology. Becker G, Darai G (eds). Berlin New York: Springer-Verlag, pp 147–156.Google Scholar
  26. Menegoz F, Little J, Colonna M, Arslan A, Preston-Martin S, Schlehofer B, Blettner M, Howe GR, Ryan P, Giles GG, Rodvall Y, Choi WN (2002). Contacts with animals and humans as risk factors for adult brain tumours. An international case-control study. Eur J Cancer 38: 696–704.PubMedCrossRefGoogle Scholar
  27. Menet A, Speth C, Larcher C, Prodinger WM, Schwendinger MG, Chan P, Jager M, Schwarzmann F, Recheis H, Fontaine M, Dierich MP (1999). Epstein-Barr virus infection of human astrocyte cell lines. J Virol 73: 7722–7733.PubMedGoogle Scholar
  28. Mocarski ES Jr (2002). Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion. Trends Microbiol 10: 332–339.PubMedCrossRefGoogle Scholar
  29. Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, Roizman B (2004). Infectious agents and cancer: criteria for a causal relation. Semin Cancer Biol 14: 453–471.PubMedCrossRefGoogle Scholar
  30. Preston-Martin S, Mack W (1996). Neoplasms of the nervous system. In: Cancer epidemiology and prevention. Schottenfield D, Fraumeni J (eds). New York: Oxford University Press, pp 1231–1291.Google Scholar
  31. Preston-Martin S, Pogoda JM, Schlehofer B, Blettner M, Howe GR, Ryan P, Menegoz F, Giles GG, Rodvall Y, Choi NW, Little J, Arslan A (1998). An international case-control study of adult glioma and meningioma: the role of head trauma. Int J Epidemiol 27: 579–586.PubMedCrossRefGoogle Scholar
  32. Rabenau HF, Buxbaum S, Preiser W, Weber B, Doerr HW (2002). Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am Main area, Germany. Med Microbiol Immunol (Berl) 190: 153–160.CrossRefGoogle Scholar
  33. RKI. (2000a). Humanes Cytomegalievirus (HCMV); Stellungnahmen des Arbeitskreises Blut des Bundesministeriums für Gesundheit. Bundesgesundheitsblatt 70: 653–659.Google Scholar
  34. RKI. (2000b). Varizellen, Herpes Zoster. Epidemiol Bull 46: 368–369.Google Scholar
  35. Rollison DE, Helzlsouer KJ, Alberg AJ, Hoffman S, Hou J, Daniel R, Shah KV, Major EO (2003). Serum antibodies to JC virus, BK virus, simian virus 40, and the risk of incident adult astrocytic brain tumors. Cancer Epidemiol Biomarkers Prev 12: 460–463.PubMedGoogle Scholar
  36. Sabatier J, Uro-Coste E, Pommepuy I, Labrousse F, Allart S, Tremoulet M, Delisle MB, Brousset P (2005). Detection of human cytomegalovirus genome and gene products in central nervous system tumours. Br J Cancer 92: 747–750.PubMedCrossRefGoogle Scholar
  37. Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS (2003). High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol 170: 998–1002.PubMedCrossRefGoogle Scholar
  38. Schlehofer B, Blettner M, Becker N, Martinsohn C, Wahrendorf J (1992). Medical risk factors and the development of brain tumors. Cancer 69: 2541–2547.PubMedCrossRefGoogle Scholar
  39. Schlehofer B, Blettner M, Preston-Martin S, Niehoff D, Wahrendorf J, Arslan A, Ahlbom A, Choi WN, Giles GG, Howe GR, Little J, Menegoz F, Ryan P (1999). Role of medical history in brain tumour development. Results from the international adult brain tumour study. Int J Cancer 82: 155–160.PubMedCrossRefGoogle Scholar
  40. Smith KO, Newman JT, Story JL, Wissinger JP (1974). Viruses and brain tumors. Clin Neurosurg 21: 362–382.PubMedGoogle Scholar
  41. Wohlrabe P, Sprossig M, Farber I, Wutzler P, Steube D, Schreiber D (1984). Virologisch-serologische Untersuchungen bei Patienten mit Hirntumoren. Zentralbl Neurochir 45: 152–158.PubMedGoogle Scholar
  42. Wolff D, Sinzger C, Drescher P, Jahn G, Plachter B (1994). Reduced levels of IE2 gene expression and shutdown of early and late viral genes during latent infection of the glioblastoma cell line U138-MG with selectable recombinants of human cytomegalovirus. Virology 204: 101–113.PubMedCrossRefGoogle Scholar
  43. Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002). Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-oncol 4: 278–299.PubMedGoogle Scholar
  44. Wrensch M, Weinberg A, Wiencke J, Masters H, Miike R, Barger G, Lee M (1997). Does prior infection with varicella-zoster virus influence risk of adult glioma? Am J Epidemiol 145: 594–597.PubMedGoogle Scholar
  45. Wrensch M, Weinberg A, Wiencke J, Miike R, Barger G, Kelsey K (2001). Prevalence of antibodies to four herpesviruses among adults with glioma and controls. Am J Epidemiol 154: 161–165.PubMedCrossRefGoogle Scholar
  46. Wutzler P, Doerr HW, Farber I, Eichhorn U, Helbig B, Sauerbrei A, Brandstadt A, Rabenau HF (2000). Seroprevalence of herpes simplex virus type 1 and type 2 in selected German populations-relevance for the incidence of genital herpes. J Med Virol 61: 201–207.PubMedCrossRefGoogle Scholar
  47. Wutzler P, Farber I, Wagenpfeil S, Bisanz H, Tischer A (2001). Seroprevalence of varicella-zoster virus in the German population. Vaccine 20: 121–124.PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2006

Authors and Affiliations

  • S. Poltermann
    • 1
    • 2
  • B. Schlehofer
    • 2
  • K. Steindorf
    • 2
  • P. Schnitzler
    • 4
  • K. Geletneky
    • 3
  • J. R. Schlehofer
    • 1
  1. 1.Division of Tumor VirologyGerman Cancer Research CenterHeidelbergGermany
  2. 2.Unit of Environmental EpidemiologyGerman Cancer Research CenterHeidelbergGermany
  3. 3.Department of NeurosurgeryUniversity of HeidelbergHeidelbergGermany
  4. 4.Department of VirologyUniversity of HeidelbergHeidelbergGermany

Personalised recommendations