Association of Human Parvovirus B19 Infection with Development and Clinical Course of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

Open access

Abstract

Our aim was to estimate the presence of B19V infection markers, the level of cytokines and time period since the appearance of infection in association with ME/CFS clinical symptoms. In 200 ME/CFS patients and 104 control group individuals the presence of B19V-specific IgG/IgM class antibodies, B19V NS1 gene sequence, mRNA expression, viral load and level of cytokines were determined. B19V-specific IgG-antibodies were found in 70% of ME/CFS patients and 67.4% of controls, IgM-antibodies in 8% of patients and in none of controls, B19V genomic sequences in 29% of patients and 3.8% of controls. 58.6% of positive patients had active and 41.4% had latent/persistent B19V infection. B19V NS1 gene expression was detected in 43% of patients. B19V load varied from < 0.2 copies to median 38.2 copies/µg of DNA. According to the antibody pattern, 36% of patients had a recent, and 43% had sustained B19V infection. Patients with the B19V genomic sequence and NS1 specific antibodies significantly more often had lymphadenopathy and multi-joint pain. Onset of the symptoms corresponded to time of appearance of B19V infection. IL-10 and TNF-levels were higher in patients with elevated B19V load. B19V genome 1 was identified in Latvian ME/CFS patients. The results indicated that at least in some cases B19V infection plays an important role in ME/CFS development

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Appel S. Chapman J. Shoenfeld Y. (2007). Infection and vaccination in chronic fatigue syndrome: Myth or reality? Autoimmunity40 48–53.

  • Bansal A. S. Bradley A. S. Bishop K. N. Kiani-Alikhan S. Ford B. (2012). Chronic fatigue syndrome the immune system and viral infection. Brain Behav. Immun.26 24–31.

  • Barah F. Vallely P. J. Chiswick M. L. Cleator G. M. Kerr J. R. (2001). Association of human parvovirus B19 infection with acute meningoencephalitis. Lancet358 729–730.

  • Barah F. Whiteside S. Batista S. Morris J. (2014). Neurological aspects of human parvovirus B19 infection: A systematic review. Rev. Med. Virol.24 154–168.

  • Brenu E. W. van Driel M. L. Staines D. R. Ashton K. J. Ramos S. B. Keane J. Klimas N. G. Marshall-Gradisnik S. M. (2011). Immunological abnormalities as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis. J. Transl. Med.9 81.

  • Brown K. E. Anderson S. M. Young N. S. (1993). Erythrocyte P antigen: Cellular receptor for B19 parvovirus. Science262 114–117.

  • Carruthers B. M. van de Sande M. I. De Meirleir K. L. Klimas N. G. Broderick G. Mitchell T. Staines D. Powles A. C. Speight N. Vallings R. Bateman L. Baumgarten-Austrheim B. Bell D. S. Carlo-Stella N. Chia J. Darragh A. Jo D. Lewis D. Light A. R. Marshall-Gradisbik S. Mena I. Mikovits J. A. Miwa K. Murovska M. Pall M. L. Stevens S. (2011). Myalgic encephalomyelitis: International Consensus Criteria. J. Intern. Med.270 327–338.

  • Chapenko S. Krumina A. Kozireva S. Nora Z. Sultanova A. Viksna L. Murovska M. (2006). Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome. J. Clin. Virol.37 Suppl 1 S47–51.

  • Chapenko S. Krumina A. Logina I. Rasa S. Chistjakovs M. Sultanova A. Viksna L. Murovska M. (2012). Association of active human herpesvirus-6 -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Adv. Virol.2012 205085.

  • Cooling L. L. Koerner T. A. Naides S. J. (1995). Multiple glycosphingolipids determine the tissue tropism of parvovirus B19. J. Infect. Dis.172 1198–1205.

  • Corcoran C. Hardie D. Yeats J. Smuts H. (2010). Genetic variants of human parvovirus B19 in South Africa: Circulation of three genotypes and identification of a novel subtype of genotype 1. J. Clin. Microbiol.48 137–142.

  • Cossart Y. E. Field A. M. Cant B. Widdows D. (1975). Parvovirus-like particles in human sera. Lancet1 72–73.

  • Couper K. N. Blount D. G. Riley E. M. (2008). IL-10: The master regulator of immunity to infection. J. Immunol.180 5771–5777.

  • Fremont M. Metzger K. Rady H. Hulstaert J. De Meirleir K. (2009). Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients. In Vivo23 209–213.

  • 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.

  • Guindon S. Dufayard J. F. Lefort V. Anisimova M. Hordijk W. Gascuel O. (2010). New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of PhyML 3.0. Syst. Biol.59 307–321.

  • Hemauer A. Gigler A. Searle K. Beckenlehner K. Raab U. Broliden K. Wolf H. 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.

  • Ito K. Shimizu N. Watanabe K. Saito T. Yoshioka Y. Sakane E. Tsunemine H. Akasaka H. Kodaka T. Takahashi T. (2013). Analysis of viral infection by multiplex polymerase chain reaction assays in patients with liver dysfunction. Intern. Med.52 201–211.

  • Johnston S. Brenu E. W. Staines D. Marshall-Gradisnik S. (2013). The prevalence of chronic fatigue syndrome/myalgic encephalomyelitis: A meta-analysis. Clin. Epidemiol.5 105–110.

  • Kerr J. R. (2000). Pathogenesis of human parvovirus B19 in rheumatic disease. Ann. Rheum. Dis.59 672–683.

  • Kerr J. R. (2016). The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease. J. Clin. Pathol.69 279–291.

  • Kerr J. R. Barah F. Mattey D. L. Laing I. Hopkins S. J. Hutchinson I. V. Tyrrell D. A. (2001). Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J. Gen. Virol.82 3011–3019.

  • Kerr J. R. Gough J. Richards S. C. Main J. Enlander D. McCreary M. Komaroff A. L. Chia J. K. (2010). Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J. Gen. Virol.91 893–897.

  • Kerr J. R. Tyrrell D. A. (2003). Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr. Pain Headache Rep.7 333–341.

  • Luo Y. Qiu J. (2015). Human parvovirus B19: A mechanistic overview of infection and DNA replication. Future Virol.10 155–167.

  • Magalhaes Ide M. Martins R. V. Vianna R. O. Moyses N. Afonso L. A. Oliveira S. A. Cavalcanti S. M. (2011). Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum. Mem. Inst. Oswaldo Cruz106 371–373.

  • Manaresi E. Gallinella G. Zerbini M. Venturoli S. Gentilomi G. Musiani M. (1999). IgG immune response to B19 parvovirus VP1 and VP2 linear epitopes by immunoblot assay. J. Med. Virol.57 174–178.

  • Matano S. Kinoshita H. Tanigawa K. Terahata S. Sugimoto T. (2003). Acute parvovirus B19 infection mimicking chronic fatigue syndrome. Intern. Med.42 903–905.

  • Modrow S. Dorsch S. (2002). Antibody responses in parvovirus B19 infected patients. Pathol. Biol. (Paris)50 326–331.

  • Momoeda M. Wong S. Kawase M. Young N. S. Kajigaya S. (1994). A putative nucleoside triphosphate-binding domain in the nonstructural protein of B19 parvovirus is required for cytotoxicity. J. Virol.68 8443–8446.

  • Morey A. L. Ferguson D. J. Fleming K. A. (1993). Ultrastructural features of fetal erythroid precursors infected with parvovirus B19 in vitro: Evidence of cell death by apoptosis. J. Pathol.169 213–220.

  • Morinet F. Corruble E. (2012). Chronic fatigue syndrome and viral infections. In: Snell C. R. (Ed.). An International Perspective on the Future of Research in Chronic Fatigue Syndrome. InTech Croatia pp. 1–12.

  • Munakata Y. Kato I. Saito T. Kodera T. Ishii K. K. Sasaki T. (2006). Human parvovirus B19 infection of monocytic cell line U937 and antibody-dependent enhancement. Virology345 251–257.

  • Nicolson G. L. (2002). Co-infections in fibromyalgia syndrome chronic fatigue syndrome and other chronic illnesses. Fibromyalgia Frontiers 10 5–9; 27–28.

  • Ozawa K. Ayub J. Hao Y. S. Kurtzman G. Shimada T. Young N. (1987). Novel transcription map for the B19 (human) pathogenic parvovirus. J. Virol.61 2395–2406.

  • Pfrepper K. I. Enders M. Motz M. (2005). Human parvovirus B19 serology and avidity using a combination of recombinant antigens enables a differentiated picture of the current state of infection. J. Vet. Med. B Infect. Dis. Vet. Public Health52 362–365.

  • Sanders P. Korf J. (2008). Neuroaetiology of chronic fatigue syndrome: An overview. World J. Biol. Psychiatry9 165–171.

  • Servant-Delmas A. Lefrere J. J. Morinet F. Pillet S. (2010). Advances in human B19 erythrovirus biology. J. Virol.84 9658–9665.

  • Soderlund-Venermo M. Hokynar K. Nieminen J. Rautakorpi H. Hedman K. (2002). Persistence of human parvovirus B19 in human tissues. Pathol. Biol. (Paris)50 307–316.

  • Soderlund M. Brown C. S. Spaan W. J. Hedman L. Hedman K. (1995). Epitope type-specific IgG responses to capsid proteins VP1 and VP2 of human parvovirus B19. J. Infect. Dis.172 1431–1436.

  • Takahashi Y. Murai C. Shibata S. Munakata Y. Ishii T. Ishii K. Saitoh T. Sawai T. Sugamura K. Sasaki T. (1998). Human parvovirus B19 as a causative agent for rheumatoid arthritis. Proc. Natl. Acad. Sci. USA95 8227–8232.

  • Tamura K. Stecher G. Peterson D. Filipski A. Kumar S. (2013). MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol. Biol. Evol.30 2725–2729.

  • von Poblotzki A. Hemauer A. Gigler A. Puchhammer-Stockl E. Heinz F. X. Pont J. Laczika K. Wolf H. Modrow S. (1995). Antibodies to the nonstructural protein of parvovirus B19 in persistently infected patients: Implications for pathogenesis. J. Infect. Dis.172 1356–1359.

  • Zhang L. Gough J. Christmas D. Mattey D. L. Richards S. C. Main J. 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. J. Clin. Pathol.63 156–164.

Search
Journal information
Impact Factor


CiteScore 2018: 0.3

SCImago Journal Rank (SJR) 2018: 0.137
Source Normalized Impact per Paper (SNIP) 2018: 0.192

Metrics
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 93 93 11
PDF Downloads 94 94 13