Skip to main content

Advertisement

SpringerLink
Log in

Identification of human herpesviruses 1 to 8 in Tunisian multiple sclerosis patients and healthy blood donors

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Members of the human Herpesviridae family are candidates for representing the macroenvironmental factors associated with multiple sclerosis (MS) pathogenesis. To verify the possible role of human herpesviruses (HHVs) as triggering or aggravating factors in relapsing–remitting multiple sclerosis clinical outcome, we studied the prevalence of all eight human herpesviruses in whole blood samples collected from 51 MS patients and from 51 healthy controls. The presence of DNA of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella zoster virus (VZV), Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7) and human herpesvirus 8 (HHV-8) was searched by specific nested polymerase chain reaction. HHVs were significantly more prevalent in the blood of MS patients than in those of the controls (P < 10−4). HSV-1, HSV-2, HCMV and HHV-8 were negative in both MS patients and controls samples. In MS patients, EBV, HHV-7, HHV-6 and VZV were detected in 31.3%, 33.3%, 5.8% and 7.8% of samples, respectively, compared with 3.9%, 9.8%, 1.96% and 1.96%, respectively, of samples from controls. We found a statistically significant difference only for EBV DNA and for HHV-7 DNA prevalence (P < 0.001 and P = 0.03). Although these results indicate lack of apparent association in terms of gender, type of diagnosis, symptoms, disease score and β interferon treatment between EBV or HHV-7 to MS among Tunisian patients, heterogeneity related to genetic polymorphism as well as geographical distribution of the disease and of pathogens may be of significance.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alvarez-Lafuente R, De Las Heras V, Bartolome M, Garcia-Montojo M, Arroyo R (2006) Human herpesvirus 6 and multiple sclerosis: a one-year follow-up study. Brain Pathol 16:20–27

    Article  PubMed  CAS  Google Scholar 

  • Alvarez-Lafuente R, de las Heras V, Garcia-Montojo M, Bartolome M, Arroyo R (2007) Human herpesvirus-6 and multiple sclerosis: relapsing–remitting versus secondary progressive. Mult Scler 13:578–583

    Article  PubMed  CAS  Google Scholar 

  • Âlvarez-Lafuente R, Martín-Estefanía C, De las Heras V, Castrillo C, Cour I, Picazo JJ, Varelade Seijas E, Arroyo R (2002) Prevalence of herpesvirus DNA in MS patients and healthy blood donors. Acta Neurol Scand 105:95–99

    Article  PubMed  Google Scholar 

  • Bello-Morales R, Fedetz M, Alcina A, Tabares E, Lopez-Guerrero JA (2005) High susceptibility of a human oligodendroglial cell line to herpes simplex type 1 infection. J Neurovirol 11:190–198

    Article  PubMed  CAS  Google Scholar 

  • Cepok S, Zhou D, Srivastava R, Nessler S, Stei S, Bussow K, Sommer N, Hemmer B (2005) Identification of Epstein–Barr virus proteins as putative targets of the immune response in multiple sclerosis. J Clin Invest 115:1352–1360

    PubMed  CAS  Google Scholar 

  • Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517

    Article  PubMed  CAS  Google Scholar 

  • Di Luca D, Mirandola P, Ravaioli T, Bigoni B, Cassai E (1996) Distribution of HHV-6 variants in human tissues. Infect Ag Dis 5:203–214

    CAS  Google Scholar 

  • Ferrante P, Omodeo-Zorini E, Zuffolato MR, Mancuso R, Caldarelli-Stefano R, Puricelll S, Mediati M, Losciale I, Caput (1997) Human T-cell lymphotropic virus tax and Epstein–Barr virus DNA in peripheral blood of multiple sclerosis patients during acute attack. Acta Neurol Scand 169:79–85

    Article  CAS  Google Scholar 

  • Ferrante P, Mancuso R, Pagani E, Guerini FR, Calvo MG, Saresella M, Speciale L, Caputo D (2000) Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack. J Neurovirol 6:S109–S114

    PubMed  CAS  Google Scholar 

  • Gardell JL, Dazin P, Islar J, Menge T, Genai CP, Lalive PH (2006) Apoptotic effects of human herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity. J Clin Virol 37:S11–S16

    Article  PubMed  CAS  Google Scholar 

  • Giovannoni G, Ebers G (2007) Multiple sclerosis: the environment and causation. Curr Opin Neurol 20:261–268

    Article  PubMed  Google Scholar 

  • Giovannoni G, Cutter GR, Lunemann J, Martin R, Münz C, Sriram S, Steiner I, Hammerschlag MR, Gaydos CA (2006) Infectious causes of multiple sclerosis. Lancet Neurol 5:887–894

    Article  PubMed  Google Scholar 

  • Gold R, Hartung HP (2005) Towards individualised multiple sclerosis therapy. Lancet Neurol 4:693–694

    Article  PubMed  Google Scholar 

  • Haahr S, Koch-Henriksen N, Mùller-Larsen A, Eriksen LS, Andersen HMK (1995) Increased risk of multiple sclerosis after late Epstein–Barr virus infection: a historical prospective study. Mult Scler 1:73–77

    PubMed  CAS  Google Scholar 

  • Hawkes CH, Giovannoni G, Keir G, Cunnington M, Thompson EJ (2006) Seroprevalence of herpes simplex virus type 2 in multiple sclerosis. Acta Neurol Scand 114:363–367

    Article  PubMed  CAS  Google Scholar 

  • Huang LM, Lee CY, Lee PI, Chen JM, Wang PJ (1991) Meningitis caused by human herpesvirus-6. Arch Dis Child 66:1443–1444

    Article  PubMed  CAS  Google Scholar 

  • Ishiguro N, Yamada S, Takahashi T, Takahashi Y, Togashi T, Okuno T, Yamanishi K (1990) Meningoencephalitis associated with HHV-6 related exanthema subitum. Acta Pediatr Scand 79:987–989

    Article  CAS  Google Scholar 

  • Kang JH, Sheu JJ, Kao S, Lin HC (2011) Increased risk of multiple sclerosis following herpes zoster: a nationwide, population-based study. J Infect Dis 204:188–192

    Article  PubMed  Google Scholar 

  • Kim JS, Lee KS, Park JH, Kim MY, Shin WS (2000) Detection of human herpesvirus 6 variant A in peripheral blood mononuclear cells from multiple sclerosis patients. Eur Neurol 43:170–173

    Article  PubMed  CAS  Google Scholar 

  • Lindsey JW, Patel S, Zou J (2008) Epstein–Barr virus genotypes in multiple sclerosis. Acta Neurol Scand 117:141–144

    PubMed  CAS  Google Scholar 

  • Lindsey JW, Hatfield LM, Crawford MP, Patel S (2009) Quantitative PCR for Epstein–Barr virus DNA and RNA in multiple sclerosis. Mult Scler 15:153–158

    Article  PubMed  CAS  Google Scholar 

  • Lucchinetti C, Brueck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717

    Article  PubMed  CAS  Google Scholar 

  • Lunemann JD, Edwards N, Muraro PA, Hayashi S, Cohen J, Münz C, Martin R (2006) Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis. Brain 129:1493–1506

    Article  PubMed  Google Scholar 

  • Mancuso R, Delbue S, Borghi E, Pagani E, Calvo MG, Caputo D, Granieri E, Ferrante P (2007) Increased prevalence of varicella zoster virus DNA in cerebrospinal fluid from patients with multiple sclerosis. J Med Virol 79:192–199

    Article  PubMed  CAS  Google Scholar 

  • Marrie RA, Wolfson C (2001) Multiple sclerosis and varicella zoster virus infection: a review. Epidemiol Infect 127:315–325

    Article  PubMed  CAS  Google Scholar 

  • Martınez A, Alvarez-Lafuente R, Mas A, Bartolomé M, García-Montojo M, De las Heras V, De la Concha E, Arroyo R, Urcelay E (2007) Environment–gene interaction in multiple sclerosis: human herpesvirus 6 and MHC2TA. Hum Immunol 68:685–689

    Article  PubMed  Google Scholar 

  • Munch M, Hvas J, Christensen T, Moller-Larsen A, Haahr S (1998a) A single subtype of Epstein–Barr virus in members of multiple sclerosis clusters. Acta Neurol Scand 98:395–399

    Article  PubMed  CAS  Google Scholar 

  • Munch M, Riisom K, Christensen T, Moller-Larsen A, Haahr S (1998b) The significance of Epstein–Barr virus seropositivity in multiple sclerosis patients? Acta Neurol Scand 97:171–174

    Article  PubMed  CAS  Google Scholar 

  • Nielsen TR, Pedersen M, Rostgaard K, Frisch M, Hjalgrim H (2007) Correlations between Epstein–Barr virus antibody levels and risk factors for multiple sclerosis in healthy individuals. Mult Scler 13:420–423

    Article  PubMed  CAS  Google Scholar 

  • Ranger S, Patillaud S, Denis F, Himmich A, Sangare A, M’Boup S, Itoua-N’Gaporo A, Prince-David M, Chout R, Cevallos R, Agut H (1991) Seroepidemiology of human herpesvirus-6 in pregnant women from different parts of the world. J Med Virol 34:194–198

    Article  PubMed  CAS  Google Scholar 

  • Rotola A, Cassai E, Tola MR, Granieri E, Di Luca D (1999) Human herpesvirus 6 is latent in peripheral blood of patients with relapsing–remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 67:529–531

    Article  PubMed  CAS  Google Scholar 

  • Rotola A, Caselli E, Cassai E, Tola MR, Granieri E, Di Luca D (2000) Novel human herpesviruses and multiple sclerosis. J Neurovirol 6:88–91

    Google Scholar 

  • Soldan SS, Berti R, Salem N, Secchiero P, Flamand L, Calabresi PA, Brennan MB, Maloni HW, Mc Farland HF, Lin HC, Patnaik M, Jacobson S (1997) Association of human herpesvirus type 6 with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat Med 3:1394–1397

    Article  PubMed  CAS  Google Scholar 

  • Soldan SS, Leist TP, Juhng KN, McFarland HF, Jacobson S (2000) Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients. Ann Neurol 47:306–313

    Article  PubMed  CAS  Google Scholar 

  • Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747

    Article  PubMed  CAS  Google Scholar 

  • Sotelo J, Ordonez G, Pineda B (2007) Varicella-zoster virus at relapses of multiple sclerosis. J Neurol 254:493–500

    Article  PubMed  Google Scholar 

  • Taus C, Pucci E, Cartechini E, Fie A, Giuliani G, Clementi M, Menzo S (2000) Absence of HHV-6 and HHV-7 in cerebrospinal fluid in relapsing–remitting multiple sclerosis. Acta Neurol Scand 101:224–228

    Article  PubMed  CAS  Google Scholar 

  • Tomsone V, Logina I, Millers A, Chapenko S, Kozireva S, Murovska M (2001) Association of human herpesvirus 6 and human herpesvirus 7 with demyelinating diseases of the nervous system. J Neurovirol 7:564–569

    Article  PubMed  CAS  Google Scholar 

  • Zivadinov R, Nasuelli D, Tommasi MA, Serafin M, Bratina A, Ukmar M, Pirko I, Aaron J, Furlan C, Pozzi-Mucelli R, Monti-Bragadin L, Grop A, Zambon M, Rodolfo A, Cazzato G, Zorzon M (2006) Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients. Neurol Res 28:262–269

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from Federazione Italiana Sclerosi Multipla 2008, Programma Ricerca Regione Università 2007/2009 and Fondi Ateneo per la Ricerca Università di Ferrara.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Laboratory of Transmissible Diseases and Biological Active substances, LR99-ES27, Faculty of Pharmacy, University of Monastir, Avicenne street 5000, Monastir, Tunisia

    Nadia Ben Fredj, Faten Nefzi & Mahjoub Aouni

  2. Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy

    Antonella Rotola, Roberta Rizzo, Elisabetta Caselli & Dario Di Luca

  3. Department of Neurology, Fattouma Bourguiba University Hospital, Monastir, Tunisia

    Saber Chebel & Mahbouba Frih-Ayed

Authors
  1. Nadia Ben Fredj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonella Rotola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faten Nefzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saber Chebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberta Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elisabetta Caselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mahbouba Frih-Ayed
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dario Di Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mahjoub Aouni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nadia Ben Fredj.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ben Fredj, N., Rotola, A., Nefzi, F. et al. Identification of human herpesviruses 1 to 8 in Tunisian multiple sclerosis patients and healthy blood donors. J. Neurovirol. 18, 12–19 (2012). https://doi.org/10.1007/s13365-011-0056-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-011-0056-z

Keywords

Search

Navigation