Skip to main content
SpringerLink
Log in

The Role of Epstein-Barr Virus in Atherosclerosis and Related Diseases

  • Chapter
  • First Online:
Viruses and Atherosclerosis

Part of the book series: SpringerBriefs in Immunology ((BRIEFSIMMUN,volume 4))

Abstract

A hypothesis of the possible role of Epstein-Barr virus (EBV) in the etiology of atherosclerosis has been proposed almost 30 years ago. The possible mechanisms of this connection can include induction and/or promotion of the proliferation of artery wall intimal smooth muscle cells by inflammatory injury or induction of genomic alterations leading to clonal expansion of intimal smooth muscle cell populations. In this review, we analyzed the feasible association between EBV and atherosclerosis. The results of certain investigators support the point of view that EBV-infection may influence the development of atherosclerosis; however, the majority of studies disprove this hypothesis. Almost all the studies where the positive association was found should not be established as entirely credible. Moreover, contradicting results were observed even in the same populations that refutes the hypothesis about the population dependence on the association between EBV and atherosclerosis. On the whole, the situation with the feasible association between EBV and atherosclerosis seems to be following: albeit there is a number of basic mechanisms supporting this hypothesis, current epidemiological data do not evidence in favor of this association. At the moment, it is not possible to establish EBV as a probable causative agent of atherosclerosis until reliable epidemiological studies devoted to the problem will confirm this hypothesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964;1:702–3.

    Article  PubMed  CAS  Google Scholar 

  2. Middeldorp JM, Brink AA, Van Den Brule AJ, Meijer CJ. Pathogenic roles for Epstein-Barr virus (EBV) gene products in EBV-associated proliferative disorders. Crit Rev Oncol Hematol. 2003;45:1–36.

    Article  PubMed  Google Scholar 

  3. Thompson MP, Kurzrock R. Epstein-Barr virus and cancer. Clin Cancer Res. 2004;10: 803–21.

    Article  PubMed  CAS  Google Scholar 

  4. Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004;4:757–68.

    Article  PubMed  CAS  Google Scholar 

  5. Kikuta H, Taguchi Y, Tomizawa K, Kojima K, Kawamura N, Ishizaka A, Sakiyama Y, Matsumoto S, Imai S, Kinoshita T. Epstein-Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease. Nature. 1988;333:455–7.

    Article  PubMed  CAS  Google Scholar 

  6. Jones JF, Shurin S, Abramowsky C, Tubbs RR, Sciotto CG, Wahl R, Sands J, Gottman D, Katz BZ, Sklar J. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med. 1988;318:733–41.

    Article  PubMed  CAS  Google Scholar 

  7. Kawaguchi H, Miyashita T, Herbst H, Niedobitek G, Asada M, Tsuchida M, Hanada R, Kinoshita A, Sakurai M, Kobayashi N. Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome. J Clin Invest. 1993;92:1444–50.

    Article  PubMed  CAS  Google Scholar 

  8. Jones K, Rivera C, Sgadari C, Franklin J, Max EE, Bhatia K, Tosato G. Infection of human endothelial cells with Epstein-Barr virus. J Exp Med. 1995;182:1213–21.

    Article  PubMed  CAS  Google Scholar 

  9. Koide J, Takada K, Sugiura M, Sekine H, Ito T, Saito K, Mori S, Takeuchi T, Uchida S, Abe T. Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient. J Virol. 1997;71:2478–81.

    PubMed  CAS  Google Scholar 

  10. Severa M, Giacomini E, Gafa V, Anastasiadou E, Rizzo F, Corazzari M, Romagnoli A, Trivedi P, Fimia GM, Coccia EM. EBV stimulates TLR- and autophagy-dependent pathways and impairs maturation in plasmacytoiddendritic cells: implications for viral immune escape. Eur J Immunol. 2012 [Epub ahead of print].

    Google Scholar 

  11. Benditt EP, Barrett T, McDougall JK. Viruses in the etiology of atherosclerosis. Proc Natl Acad Sci U S A. 1983;80:6386–9.

    Article  PubMed  CAS  Google Scholar 

  12. Yamashiroya HM, Ghosh L, Yang R, Robertson Jr AL. Herpesviridae in the coronary arteries and aorta of young trauma victims. Am J Pathol. 1988;130:71–9.

    PubMed  CAS  Google Scholar 

  13. Musiani M, Zerbini ML, Muscari A, Puddu GM, Gentilomi G, Gibellini D, Gallinella G, Puddu P, La Placa M. Antibody patterns against cytomegalovirus and Epstein-Barr virus in human atherosclerosis. Microbiologica. 1990;13:35–41.

    PubMed  CAS  Google Scholar 

  14. Straka F, Málek I, Stanĕk V, Ouhrabková R, Gebauerová M, Urbanová D, Vrubel J, Pirk J, Zelízko M, Lánská V. Coronary disease in patients after heart transplantation. Cor Vasa. 1993;35:267–75.

    PubMed  CAS  Google Scholar 

  15. Delneste Y, Lassalle P, Jeannin P, Mannessier L, Dessaint JP, Joseph M, Tonnel AB. Production of anti-endothelial cell antibodies by coculture of EBV-infected human B cells with endothelial cells. Cell Immunol. 1993;150:15–26.

    Article  PubMed  Google Scholar 

  16. Tanaka S, Komori K, Okadome K, Sugimachi K, Mori R. Detection of active cytomegalovirus infection in inflammatory aortic aneurysms with RNA polymerase chain reaction. J Vasc Surg. 1994;20:235–43.

    Article  PubMed  CAS  Google Scholar 

  17. Luo CY, Ko WC, Tsao CJ, Yang YJ, Su IJ. Epstein-Barr virus-containing T-cell lymphoma and atherosclerotic abdominal aortic aneurysm in a young adult. Hum Pathol. 1999;30:1114–7.

    Article  PubMed  CAS  Google Scholar 

  18. Horváth R, Cerný J, Benedík Jr J, Hökl J, Jelínková I, Benedík J. The possible role of human cytomegalovirus (HCMV) in the origin of atherosclerosis. J Clin Virol. 2000;16:17–24.

    Article  PubMed  Google Scholar 

  19. Rupprecht HJ, Blankenberg S, Bickel C, Rippin G, Hafner G, Prellwitz W, Schlumberger W, Meyer J, AutoGene Investigators. Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation. 2001;104:25–31.

    Article  PubMed  CAS  Google Scholar 

  20. Espinola-Klein C, Rupprecht HJ, Blankenberg S, Bickel C, Kopp H, Victor A, Hafner G, Prellwitz W, Schlumberger W, Meyer J. Impact of infectious burden on progression of carotid atherosclerosis. Stroke. 2002;33:2581–6.

    Article  PubMed  CAS  Google Scholar 

  21. Espinola-Klein C, Rupprecht HJ, Blankenberg S, Bickel C, Kopp H, Rippin G, Victor A, Hafner G, Schlumberger W, Meyer J, AtheroGene Investigators. Impact of infectious burden on extent and long-term prognosis of atherosclerosis. Circulation. 2002;105:15–21.

    Article  PubMed  Google Scholar 

  22. Shi Y, Tokunaga O. Herpesvirus (HSV-1, EBV and CMV) infections in atherosclerotic compared with non-atherosclerotic aortic tissue. Pathol Int. 2002;52:31–9.

    Article  PubMed  Google Scholar 

  23. De Backer J, Mak R, De Bacquer D, Van Renterghem L, Verbraekel E, Kornitzer M, De Backer G. Parameters of inflammation and infection in a community based case-control study of coronary heart disease. Atherosclerosis. 2002;160:457–63.

    Article  PubMed  Google Scholar 

  24. Khairy P, Rinfret S, Tardif JC, Marchand R, Shapiro S, Brophy J, Dupuis J. Absence of association between infectious agents and endothelial function in healthy young men. Circulation. 2003;107:1966–71.

    Article  PubMed  Google Scholar 

  25. Pitiriga VC, Kotsis VT, Alexandrou ME, Petrocheilou-Paschou VD, Kokolakis N, Zakopoulou RN, Zakopoulos NA. Increased prevalence of Chlamydophila pneumoniae but not Epstein-Barr antibodies in essential hypertensives. J Hum Hypertens. 2003;17:21–7.

    Article  PubMed  Google Scholar 

  26. Pitiriga VC, Kotsis VT, Gennimata V, Alexandrou ME, Papamichail CM, Mitsibounas DN, Petrocheilou-Paschou VD, Zakopoulos NA. Chlamydia pneumoniae and Epstein-Barr antibodies are not associated with carotid thickness: the effect of hypertension. Am J Hypertens. 2003;16:777–80.

    Article  PubMed  Google Scholar 

  27. Andrié R, Braun P, Heinrich KW, Lüderitz B, Bauriedel G. Prevalence of intimal pathogen burden in acute coronary syndromes. Z Kardiol. 2003;92:641–9.

    Article  PubMed  Google Scholar 

  28. Kwon TW, Kim DK, Ye JS, Lee WJ, Moon MS, Joo CH, Lee H, Kim YK. Detection of enterovirus, cytomegalovirus, and Chlamydia pneumoniae in atheromas. J Microbiol. 2004;42:299–304.

    PubMed  CAS  Google Scholar 

  29. Ibrahim AI, Obeid MT, Jouma MJ, Moasis GA, Al-Richane WL, Kindermann I, Boehm M, Roemer K, Mueller-Lantzsch N, Gärtner BC. Detection of herpes simplex virus, cytomegalovirus and Epstein-Barr virus DNA in atherosclerotic plaques and in unaffected bypass grafts. J Clin Virol. 2005;32:29–32.

    Article  PubMed  CAS  Google Scholar 

  30. Lobzin IV, Boĭtsov SA, Filippov AE, Linchak RM, Mangutov DA. Effect of respiratory infections on the clinical course of coronary artery disease. Klin Med (Mosk). 2005;83:22–6.

    Google Scholar 

  31. Schlitt A, Blankenberg S, Weise K, Gärtner BC, Mehrer T, Peetz D, Meyer J, Darius H, Rupprecht HJ. Herpesvirus DNA (Epstein-Barr virus, herpes simplex virus, cytomegalovirus) in circulating monocytes of patients with coronary artery disease. Acta Cardiol. 2005;60:605–10.

    Article  PubMed  Google Scholar 

  32. Lenzi C, Palazzuoli A, Giordano N, Alegente G, Gonnelli C, Campagna MS, Santucci A, Sozzi M, Papakostas P, Rollo F, Nuti R, Figura N. H. pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients withcoronary heart disease. World J Gastroenterol. 2006;12:7815–20.

    PubMed  CAS  Google Scholar 

  33. Altun B, Rota S, Demircin M, Reşatoğlu A, Yener A, Bozdayi G. Investigation of herpes group and hepatitis A virus nucleic acids in the atherome plaque samples of patients with coronary arterial disease. Mikrobiyol Bul. 2007;41:537–44.

    PubMed  Google Scholar 

  34. Bayram A, Erdoğan MB, Ekşi F, Yamak B. Demonstration of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Cytomegalovirus, and Epstein-Barr virus in atherosclerotic coronary arteries, nonrheumatic calcific aortic and rheumaticstenotic mitral valves by polymerase chain reaction. Anadolu Kardiyol Derg. 2011;11:237–43.

    PubMed  Google Scholar 

  35. Tremolada S, Delbue S, Ferraresso M, Carloni C, Elia F, Larocca S, Bortolani E, Ferrante P. Search for genomic sequences of microbial agents in atherosclerotic plaques. Int J Immunopathol Pharmacol. 2011;24:243–6.

    PubMed  CAS  Google Scholar 

  36. Valmary S, Dorfmüller P, Montani D, Humbert M, Brousset P, Degano B. Human γ-herpes viruses Epstein-Barr virus and human herpesvirus-8 are not detected in the lungs of patients with severe pulmonary arterial hypertension. Chest. 2011;139:1310–6.

    Article  PubMed  Google Scholar 

  37. de Boer OJ, Teeling P, Idu MM, Becker AE, van der Wal AC. Epstein Barr virus specific T-cells generated from unstable human atherosclerotic lesions: implications for plaque inflammation. Atherosclerosis. 2006;184:322–9.

    Article  PubMed  Google Scholar 

  38. Herrero JA, Mathew P, Paya CV. LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha. J Virol. 1995;69:2168–74.

    PubMed  CAS  Google Scholar 

  39. McColl SR, Roberge CJ, Larochelle B, Gosselin J. EBV induces the production and release of IL-8 and macrophage inflammatory protein-1 alpha in human neutrophils. J Immunol. 1997;159:6164–8.

    PubMed  CAS  Google Scholar 

  40. Waldman WJ, Williams Jr MV, Lemeshow S, Binkley P, Guttridge D, Kiecolt-Glaser JK, Knight DA, Ladner KJ, Glaser R. Epstein-Barr virus-encoded dUTPase enhances proinflammatory cytokine production by macrophages in contact with endothelial cells: evidence for depression-induced atherosclerotic risk. Brain Behav Immun. 2008;22:215–23.

    Article  PubMed  CAS  Google Scholar 

  41. Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998;128:127–37.

    Article  PubMed  CAS  Google Scholar 

  42. Kempe S, Heinz P, Kokai E, Devergne O, Marx N, Wirth T. Epstein-Barr virus-induced gene-3 is expressed in human atheroma plaques. Am J Pathol. 2009;175:440–7.

    Article  PubMed  CAS  Google Scholar 

  43. Apostolou F, Gazi IF, Lagos K, Tellis CC, Tselepis AD, Liberopoulos EN, Elisaf M. Acute infection with Epstein-Barr virus is associated with atherogenic lipid changes. Atherosclerosis. 2010;212:607–13.

    Article  PubMed  CAS  Google Scholar 

  44. Andrié RP, Bauriedel G, Tuleta I, Braun P, Nickenig G, Skowasch D. Impact of intimal pathogen burden in acute coronary syndromes–correlation with inflammation, thrombosis, and autoimmunity. Cardiovasc Pathol. 2010;19:e205–10.

    Article  PubMed  Google Scholar 

  45. Al-Ghamdi A. Role of herpes simplex virus-1, cytomegalovirus and Epstein-Barr virus in atherosclerosis. Pak J Pharm Sci. 2012;25:89–97.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Epidemiology, Kemerovo State Medical Academy, Kemerovo, Russia

    Anton Kutikhin & Elena Brusina

  2. Res Inst Cardiovascular Diseases, Russian Academy of Medical Sciences Siberian Branch, Kemerovo, Russia

    Arseniy E. Yuzhalin

  3. Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, UK, OX3 7DQ

    Arseniy E. Yuzhalin

Authors
  1. Anton Kutikhin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Brusina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arseniy E. Yuzhalin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kutikhin, A., Brusina, E., Yuzhalin, A.E. (2013). The Role of Epstein-Barr Virus in Atherosclerosis and Related Diseases. In: Viruses and Atherosclerosis. SpringerBriefs in Immunology, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8863-7_3

Download citation

Publish with us

Policies and ethics

Search

Navigation