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RNA Viruses and Autoimmunity: A Short Overview

  • Massimo Galli
  • Giorgio Bozzi
  • Andrea Giacomelli
Chapter

Abstract

RNA viruses are a large group of widespread and extremely prevalent pathogens capable of eliciting a broad spectrum of innate and adaptive immune responses. Additionally, persistent infection by some RNA viruses can induce or enhance accelerated immune activation. The hypothesis that molecular mimicry is implicated in autoimmunity was first proposed in 1987. Since then, a growing evidence from medical literature of a possible role for viral infection in autoimmunity has risen. In particular, enteroviruses have been investigated as possible causes of type 1 diabetes. Some hypotheses have put forward the possible implication of hepatitis A virus in autoimmune phenomena. The two most prevalent RNA viruses causing chronic infection, hepatitis C virus and human immunodeficiency virus type 1 (HIV-1), are both associated with autoimmune disorders. HCV can trigger and sustain a clonal B-cell expansion which causes a wide spectrum of autoimmune/lymphoproliferative disorders, through a multistep process. Similarly, HIV is responsible for derangement of the immune regulation and is associated with some autoimmune disorders, such as autoimmune thrombocytopenia. Nevertheless, a formal scientific demonstration of an etiological relationship between any RNA virus and a major autoimmune disease has not yet been obtained.

Keywords

Hepatitis A virus Hepatitis C virus Enterovirus Human immunodeficiency virus Cryoglobulinemia 

Abbreviations

AHA

Autoimmune hemolytic anemia

AIDS

Acquired immunodeficiency syndrome

ANA

Antinuclear antibody

Anti-LKM

Anti-liver/kidney microsomal antibodies

CA

Coxsackie A viruses

cART

Combined antiretroviral therapy

CB

Coxsackie B viruses

CD4+ T cells

Helper T lymphocytes

CV

Cryoglobulinemic vasculitis

DCM

Dilated cardiomyopathy

DM

Dermatomyositis

GAD65

Glutamic acid decarboxylase autoantigen

MGN

Membranoproliferative glomerulonephritis

HAV

Hepatitis A virus

HCV

Hepatitis C virus

HIV-1

Human immunodeficiency virus type 1

IRIS

Immune restoration inflammatory syndrome

PM

Polymyositis

PsA

Psoriatic arthritis

RA

Rheumatoid arthritis

RNA

Ribonucleic acid

SLE

Systemic lupus erythematosus

T1D

Type 1 diabetes

TCR

T-cell receptor

References

  1. 1.
    Oberste MS, Maher K, Kilpatrick DR, Pallansch MA. Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol. 1999;73(3):1941–8.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Vreugdenhil GR, Geluk A, Ottenhoff TH, Melchers WJ, Roep BO, Galama JM. Molecular mimicry in diabetes mellitus: the homologous domain in coxsackie B virus protein 2C and islet autoantigen GAD65 is highly conserved in the coxsackie B-like enteroviruses and binds to the diabetes associated HLA-DR3 molecule. Diabetologia. 1998;41(1):40–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Massilamany C, Koenig A, Reddy J, Huber S, Buskiewicz I. Autoimmunity in picornavirus infections. Curr Opin Virol. 2016;16:8–14.CrossRefPubMedGoogle Scholar
  4. 4.
    Coppieters KT, Boettler T, von Herrath M. Virus infections in type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(1):a007682.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Jaïdane H, Hober D. Role of coxsackievirus B4 in the pathogenesis of type 1 diabetes. Diabetes Metab. 2008;34(6 Pt 1):537–48.CrossRefPubMedGoogle Scholar
  6. 6.
    Huber SA. Viral myocarditis and dilated cardiomyopathy: etiology and pathogenesis. Curr Pharm Des. 2016;22(4):408–26.CrossRefPubMedGoogle Scholar
  7. 7.
    Cihakova D, Rose NR. Pathogenesis of myocarditis and dilated cardiomyopathy. Adv Immunol. 2008;99:95–114.CrossRefPubMedGoogle Scholar
  8. 8.
    Rose NR. Myocarditis: infection versus autoimmunity. J Clin Immunol. 2009;29(6):730–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Trepo C, Zoulim F, Pradat P. Viral hepatitis. Curr Opin Infect Dis. 1999;12:481–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Shalit M, Wollner S, Levo Y. Cryoglobulinemia in acute type-A hepatitis. Clin Exp Immunol. 1982;47:613–6.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Vento S, Garofano T, Di Perri G, et al. Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals. Lancet. 1991;337:1183–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Singh G, Palaniappan S, Rotimi O, Hamlin PJ. Autoimmune hepatitis triggered by hepatitis A. Gut. 2007;56:304.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cuthbert JA, Hepatitis A. Old and new. Clin Microbiol Rev. 2001;14(1):38–58. Review. Erratum in: Clin Microbiol Rev 2001;14(3):642.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lingala S, Ghany MG. Natural history of hepatitis C. Gastroenterol Clin N Am. 2015;44(4):717–34.  https://doi.org/10.1016/j.gtc.2015.07.003.CrossRefGoogle Scholar
  15. 15.
    McMurray RW, Elbourne K. Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum. 1997;26(4):689–701.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Charles ED, Dustin LB. Hepatitis C virus-induced cryoglobulinemia. Kidney Int. 2009;76(8):818–24.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis. 2014;46(Suppl 5):S165–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Paroli M, Iannucci G, Accapezzato D. Hepatitis C virus infection and autoimmune diseases. Int J Gen Med. 2012;5:903–7.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jadali Z, Alavian SM. Autoimmune diseases co-existing with hepatitis C virus infection. Iran J Allergy Asthma Immunol. 2010;9(4):191–206.PubMedGoogle Scholar
  20. 20.
    Zuckerman E, Yeshurun D, Rosner I. Management of hepatitis C virus-related arthritis. BioDrugs. 2001;15(9):573–84.CrossRefPubMedGoogle Scholar
  21. 21.
    Winchester R, Bernstein DH, Fisher HD, et al. The co-occurrence of Reiter’s syndrome and acquired immunodeficiency. Ann Intern Med. 1987;106:19–26.CrossRefPubMedGoogle Scholar
  22. 22.
    Fox C, Walker-Bone K. Evolving spectrum of HIV-associated rheumatic syndromes. Best Pract Res Clin Rheumatol. 2015;29(2):244–58.  https://doi.org/10.1016/j.berh.2015.04.019.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Marquez J, Restrepo CS, Candia L, et al. Human immunodeficiency virus-associated rheumatic disorders in the HAART era. J Rheumatol. 2004;31:741–6.PubMedGoogle Scholar
  24. 24.
    Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007;4:9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Parker R, Stein DJ, Jelsma J. Pain in people living with HIV/AIDS: a systematic review. J Int AIDS Soc. 2014;17(1):18719.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Oldstone MB, et al. Cell. 1987;50(6):819–20. Erratum in Cell 1987;51(5):878.CrossRefPubMedGoogle Scholar
  27. 27.
    Medina-Rodriguez F, Guzman C, Jara LJ, et al. Rheumatic manifestations in human immunodeficiency virus positive and negative individuals: a study of 2 populations with similar risk factors. J Rheumatol. 1993;20:1880–4.PubMedGoogle Scholar
  28. 28.
    Berman A, Espinoza LR, Diaz JD, et al. Rheumatic manifestations of human immunodeficiency virus infection. Am J Med. 1988;85:59–64.CrossRefPubMedGoogle Scholar
  29. 29.
    Kole AK, Roy R, Kole DC. Musculoskeletal and rheumatological disorders in HIV infection: experience in a tertiary referral center. Indian J Sex Transm Dis. 2013;34(2):107–12.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Duvic M, Johnson TM, Rapini RP, et al. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol. 1987;123:1622–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Achuthan K, Uppal SS. Rheumatological manifestations in 102 cases of HIV infection. J Ind Rheum Ass. 1996;3:43–7.Google Scholar
  32. 32.
    Bijlsma JWJ, Derksen RHWM, Huber-Brunning O, Borleffs JCC. Does AIDS ‘cure’ rheumatoid arthritis? Ann Rheum Dis. 1988;47:350–1.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Rigante D, Mazzoni MB, Esposito S. The cryptic interplay between systemic lupus erythematosus and infections. Autoimmun Rev. 2014;13:96–102.CrossRefPubMedGoogle Scholar
  34. 34.
    Martinez V, Diemert MC, Braibant M, ALT ANRS CO15 Study Group, et al. Anticardiolipin antibodies in HIV infection are independently associated with antibodies to the membrane proximal external region of gp41 and with cell-associated HIV DNA and immune activation. Clin Infect Dis. 2009;48(1):123–32.  https://doi.org/10.1086/595013.CrossRefPubMedGoogle Scholar
  35. 35.
    Itescu S, Brancato LJ, Winchester R. A sicca syndrome in HIV infection: association with HLA-DR5 and CD8 lymphocytosis. Lancet. 1989;2(8661):466–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Basu D, Williams F, Ahn C, Reveille J. Changing spectrum of the diffuse infiltrative lymphocytosis syndrome. Arthritis Rheum. 2006;55(3):466–72.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Guillevin L. Vasculitides in the context of HIV infection. AIDS. 2008;22(Suppl. 3):S27–33.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Galli M, Musicco M, Gervasoni C, et al. No evidence of a higher risk of progression to AIDS in patients with HIV-1-related severe thrombocytopenia. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12(3):268–75.CrossRefPubMedGoogle Scholar
  39. 39.
    Franzetti M, Adorni F, Oreni L, et al. Changes in the incidence of severe thrombocytopenia and its predisposing conditions in HIV-infected patients since the introduction of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;67(5):493–8.  https://doi.org/10.1097/QAI.0000000000000347.CrossRefPubMedGoogle Scholar
  40. 40.
    Ambler KL, Vickars LM, Leger CS, et al. Clinical features, treatment, and outcome of HIV-associated immune thrombocytopenia in the HAART era. Adv Hematol. 2012;2012:910954.  https://doi.org/10.1155/2012/910954.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Lenner R, Bregman Z, Teirstein AS, DePalo L. Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active antiretroviral therapy. Chest. 2001;119(3):978–81.CrossRefPubMedGoogle Scholar
  42. 42.
    Chen F, Day SL, Metcalfe RA, Sethi G, Kapembwa MS, Brook MG, et al. Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease. Medicine (Baltimore). 2005;84(2):98–106.CrossRefGoogle Scholar
  43. 43.
    Murunga E, Andersson M, Rensburg C. Autoimmune hepatitis: manifestation of immune reconstitution inflammatory syndrome in HIV infected patients? Scand J Gastroenterol. 2016;51(7):814–8.  https://doi.org/10.3109/00365521.2016.1157888.CrossRefPubMedGoogle Scholar
  44. 44.
    Maurer TA, Zackheim HS, Tuffanelli L, Berger TG. The use of methotrexate for treatment of psoriasis in patients with HIV infection. J Am Acad Dermatol. 1994;31:372–5.CrossRefPubMedGoogle Scholar
  45. 45.
    Sperber K, Kalb TH, Stecher VJ, Banerjee R, Mayer L. Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes. AIDS Res Hum Retrovir. 1993;9:91–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Castillo JJ, Echenique IA. Rituximab in combination with chemotherapy versus chemotherapy alone in HIV associated non-Hodgkin lymphoma: a pooled analysis of 15 prospective studies. Am J Hematol. 2012;87:330–3.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Massimo Galli
    • 1
  • Giorgio Bozzi
    • 1
  • Andrea Giacomelli
    • 1
  1. 1.Infectious Diseases UnitUniversity of Milan, L. Sacco HospitalMilanItaly

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