1887

Abstract

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a neuro-immune disease of uncertain pathogenesis. Human parvovirus B19 infection has been shown to occur just prior to development of the onset of CFS/ME in several cases, although B19 seroprevalence studies do not show any significant differences between CFS/ME and controls. In this study, we analysed parvovirus B19 markers in CFS/ME patients (=200), diagnosed according to Fukuda CDC criteria, and normal blood donors (=200). Serum from each subject was tested for anti-B19 VP2 IgM and IgG (by Biotrin ELISA), anti-B19 NS1 IgM and IgG (by immunofluorescence), and B19 DNA (by real-time PCR). CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG ( =64.8; <0.0001; odds ratio=9.42, CI 5.11–17.38). Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR ( =9.35, <0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes and . As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.017590-0
2010-04-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/4/893.html?itemId=/content/journal/jgv/10.1099/vir.0.017590-0&mimeType=html&fmt=ahah

References

  1. Astell, C. R., Weixing, L., Brunstein, J. & Amand, J. S.(1997). The genome of B19 parvovirus. In Human Parvovirus B19.Monographs in Virology, vol. 20, pp. 16–41. Edited by L. J. Anderson & N. S. Young. New York: Karger.
  2. Chalder, T., Berelowitz, G., Pawlikowska, T., Watts, L., Wessely, S., Wright, D. & Wallace, E. P.(1993). Development of a fatigue scale. J Psychosom Res 37, 147–153.[CrossRef] [Google Scholar]
  3. Devanur, L. D. & Kerr, J. R.(2006). Chronic fatigue syndrome. J Clin Virol 37, 139–150.[CrossRef] [Google Scholar]
  4. Fu, Y., Ishii, K. K., Munakata, Y., Saitoh, T., Kaku, M. & Sasaki, T.(2002). Regulation of tumor necrosis factor alpha promoter by human parvovirus B19 NS1 through activation of AP-1 and AP-2. J Virol 76, 5395–5403.[CrossRef] [Google Scholar]
  5. Fukuda, K., Straus, S. E., Hickie, I., Sharpe, M. C., Dobbins, J. G. & Komaroff, A.(1994). The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121, 953–959.[CrossRef] [Google Scholar]
  6. Gareus, R., Gigler, A., Hemauer, A., Leruez-Ville, M., Morinet, F., Wolf, H. & Modrow, S.(1998). Characterization of cis-acting and NS1-responsive elements in the p6 promoter of parvovirus B19. J Virol 72, 609–616. [Google Scholar]
  7. Hemauer, A., Modrow, S., Georgi, J., Helmke, K., Veith, P., Lang, B., Schölmerich, J. & Straub, R. H.(1999). There is no association between polymyalgia rheumatica and acute parvovirus B19 infection. Ann Rheum Dis 58, 657[CrossRef] [Google Scholar]
  8. Hemauer, A., Gigler, A., Searle, K., Beckenlehner, K., Raab, U., Broliden, K., Enders, G. & Modrow, S.(2000). Seroprevalence of parvovirus B19 NS1-specific IgG in B19-infected and uninfected individuals and in infected pregnant women. J Med Virol 60, 48–55.[CrossRef] [Google Scholar]
  9. Hicks, K. E., Cubel, R. C., Cohen, B. J. & Clewley, J. P.(1996). Sequence analysis of a parvovirus B19 isolate and baculovirus expression of the non-structural protein. Arch Virol 141, 1319–1327.[CrossRef] [Google Scholar]
  10. Kaushik, N., Fear, D., Richards, S. C., McDermott, C. R., Nuwaysir, E. F., Kellam, P., Harrison, T. J., Wilkinson, R. J., Tyrrell, D. A. & other authors(2005). Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. J Clin Pathol 58, 826–832.[CrossRef] [Google Scholar]
  11. Kerr, J. R. & Cunniffe, V. S.(2000). Antibodies to parvovirus B19 nonstructural protein are associated with chronic but not acute arthritis following B19 infection. Rheumatology 39, 903–908.[CrossRef] [Google Scholar]
  12. Kerr, J. R. & Modrow, S.(2006). Human parvovirus B19. In The Parvoviruses, pp. 385–416. Edited by J. R. Kerr, S. F. Cotmore, M. E. Bloom, M. Linden & C. R. Parrish. London: Hodder Arnold.
  13. Kerr, J. R., Barah, F., Mattey, D. L., Laing, I., Hopkins, S. J., Hutchinson, I. V. & Tyrrell, D. A.(2001). Circulating tumour necrosis factor-α and interferon-γ are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol 82, 3011–3019. [Google Scholar]
  14. Kerr, J. R., Bracewell, J., Laing, I., Mattey, D. L., Bernstein, R. M., Bruce, I. N. & Tyrrell, D. A.(2002). Chronic fatigue syndrome and arthralgia following parvovirus B19 infection. J Rheumatol 29, 595–602. [Google Scholar]
  15. Kerr, J. R., Cunniffe, V. S., Kelleher, P., Bernstein, R. M. & Bruce, I. N.(2003). Successful intravenous immunoglobulin (IVIG) therapy in parvovirus B19-associated chronic fatigue syndrome (CFS). Clin Infect Dis 36, e100–e106.[CrossRef] [Google Scholar]
  16. Kerr, J. R., Kaushik, N., Fear, D., Baldwin, D. A., Nuwaysir, E. F. & Adcock, I. M.(2005). Single nucleotide polymorphisms (SNPs) associated with symptomatic infection and differential human gene expression in seropositive persons implicate the cytoskeleton, integrin signalling and oncosuppression in the pathogenesis of human parvovirus B19 infection. J Infect Dis 192, 276–286.[CrossRef] [Google Scholar]
  17. Kerr, J. R., Petty, R., Burke, B., Gough, J., Fear, D., Sinclair, L. I., Mattey, D. L., Richards, S. C., Montgomery, J. & other authors(2008). Gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis 197, 1171–1184.[CrossRef] [Google Scholar]
  18. Komaroff, A. L. & Buchwald, D.(1998). Chronic fatigue syndrome: an update. Annu Rev Med 49, 1–13.[CrossRef] [Google Scholar]
  19. Lehmann, H. W., Kühner, L., Beckenlehner, K., Müller-Godeffroy, E., Heide, K. G., Küster, R. M. & Modrow, S.(2002). Chronic human parvovirus B19 infection in rheumatic disease of childhood and adolescence. J Clin Virol 25, 135–143.[CrossRef] [Google Scholar]
  20. Moffatt, S., Tanaka, N., Tada, K., Nose, M., Nakamura, M., Muraoka, O., Hirano, T. & Sugamura, K.(1996). A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression. J Virol 70, 8485–8491. [Google Scholar]
  21. Papanicolaou, D. A., Amsterdam, J. D., Levine, S., McCann, S. M., Moore, R. C., Newbrand, C. H., Allen, G., Nisenbaum, R., Pfaff, D. W. & other authors(2004). Neuroendocrine aspects of chronic fatigue syndrome. Neuroimmunomodulation 11, 65–74.[CrossRef] [Google Scholar]
  22. Raab, U., Bauer, B., Gigler, A., Beckenlehner, K., Wolf, H. & Modrow, S.(2001). Cellular transcription factors that interact with the p6 promoter elements of parvovirus B19. J Gen Virol 82, 1473–1480. [Google Scholar]
  23. Raab, U., Beckenlehner, K., Lowin, T., Niller, H. H., Doyle, S. & Modrow, S.(2002). NS1-protein of parvovirus B19 interacts directly with DNA sequences of the p6-promoter and with cellular transcription factors Sp1/Sp3. Virology 293, 86–93.[CrossRef] [Google Scholar]
  24. Reeves, W. C., Lloyd, A., Vernon, S. D., Klimas, N., Jason, L. A., Bleijenberg, G., Evengard, B., White, P. D., Nisenbaum, R. & Unger, E. R.(2003). Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res 3, 25[CrossRef] [Google Scholar]
  25. Report of the CFS/ME Working Group(2002). Department of Health, January 2002 (http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4064840).
  26. Searle, K., Schalasta, G. & Enders, G.(1998). Development of antibodies to the nonstructural protein NS1 of parvovirus B19 during acute symptomatic and subclinical infection in pregnancy: implications for pathogenesis doubtful. J Med Virol 56, 192–198.[CrossRef] [Google Scholar]
  27. Vassias, I., Hazan, U., Michel, Y., Sawa, C., Handa, H., Gouya, L. & Morinet, F.(1998). Regulation of human B19 parvovirus promoter expression by hGABP (E4TF1) transcription factor. J Biol Chem 273, 8287–8293.[CrossRef] [Google Scholar]
  28. von Poblotzki, A., Hemauer, A., Gigler, A., Puchhammer-Stöckl, E., Heinz, F. X., Pont, J., Laczika, K., Wolf, H. & Modrow, S.(1995a). Antibodies to the nonstructural protein of parvovirus B19 in persistently infected patients: implications for pathogenesis. J Infect Dis 172, 1356–1359.[CrossRef] [Google Scholar]
  29. von Poblotzki, A., Gigler, A., Lang, B., Wolf, H. & Modrow, S.(1995b). Antibodies to parvovirus B19 NS-1 protein in infected individuals. J Gen Virol 76, 519–527.[CrossRef] [Google Scholar]
  30. Zhang, L., Gough, J., Christmas, D., Mattey, D. L., Richards, S. C. M., Enlander, D., Honeybourne, D., Ayres, J. G., Nutt, D. J. & Kerr, J. R.(2010). Microbial infections in eight genomic subtypes of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). J Clin Pathol in press [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.017590-0
Loading
/content/journal/jgv/10.1099/vir.0.017590-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error