AGE

, 36:9716 | Cite as

TTV DNA plasma load and its association with age, gender, and HCMV IgG serostatus in healthy adults

  • Mats Haloschan
  • Rainer Bettesch
  • Irene Görzer
  • Lukas Weseslindtner
  • Michael Kundi
  • Elisabeth Puchhammer-Stöckl
Article

Abstract

Understanding immunosenescence and changes in antimicrobial immune response with age is of high importance. The association of immunosenescence with gender and persistent infection with human cytomegalovirus (HCMV) is a matter of intensive research. We determined whether replication of another persistent and highly prevalent virus, Torque teno virus (TTV), is related to age, gender, and HCMV IgG serostatus of the host. TTV DNA load in plasma was assessed by real-time PCR in 313 healthy persons: 20–30 years old (young, n = 104), 50–60 years old (middle-aged, n = 101), or >80 years old (elderly, n = 108). TTV DNA loads were further associated with age-groups, gender, and HCMV IgG serostatus. TTV load was significantly higher in the elderly compared to the young group (p < 0.001; Tukey’s honest significant difference (HSD)), and the higher TTV DNA levels over age were found to be gender-specific (p = 0.002; ANOVA), with young women showing the lowest TTV load compared to young men (p = 0.009, t test) and compared to the other female age-groups (middle-aged p = 0.005; elderly p < 0.001; Tukey’s HSD). TTV load of HCMV IgG-seropositive persons was significantly higher than that of the HCMV IgG seronegative in the young (p = 0.005; t test) and middle-aged (p = 0.016; t test) groups. These results indicate that the host’s immune control of TTV replication decreases with age and is gender-specific. Persistent HCMV infection is significantly related to higher TTV DNA loads, especially at a younger age. Therefore, the influence of gender and HCMV on immunosenescence earlier in life should be further explored.

Keywords

TTV Anellovirus Aging Immunosenescence Gender Cytomegalovirus 

References

  1. Aberle JH, Puchhammer-Stöckl E (2012) Age-dependent increase of memory B cell response to cytomegalovirus in healthy adults. Exp Gerontol 47(8):654–657. doi:10.1016/j.exger.2012.04.008 PubMedCrossRefGoogle Scholar
  2. Al-Moslih MI, Abuodeh RO, Hu YW (2004) Detection and genotyping of TT virus in healthy and subjects with HBV or HCV in different populations in the United Arab Emirates. J Med Virol 72(3):502–508. doi:10.1002/jmv.20017 PubMedCrossRefGoogle Scholar
  3. Ansar Ahmed S, Karpuzoglu E, Khan D (2010) Effects of sex steroids on innate and adaptive immunity. In: Klein SL, Roberts C (eds) Sex hormones and immunity to infection. Springer, Berlin, pp 19–51. doi:10.1007/978-3-642-02155-8_2 CrossRefGoogle Scholar
  4. Beland K, Dore-Nguyen M, Gagne MJ, Patey N, Brassard J, Alvarez F, Halac U (2013) Torque teno virus in children with orthotopic liver transplantation: new insights about a common pathogen. J Infect Dis. doi:10.1093/infdis/jit423 PubMedGoogle Scholar
  5. Bernardin F, Operskalski E, Busch M, Delwart E (2010) Transfusion transmission of highly prevalent commensal human viruses. Transfusion 50(11):2474–2483. doi:10.1111/j.1537-2995.2010.02699.x PubMedCrossRefGoogle Scholar
  6. Biagini P, de Micco P (2008) Anellovirus. In: Mahy BWJ, Regenmortel MHVV (eds) Encyclopedia of virology, Thirdth edn. Academic, Oxford, pp 104–110CrossRefGoogle Scholar
  7. Burra P, Masier A, Boldrin C, Calistri A, Andreoli E, Senzolo M, Zorzi M, Sgarabotto D, Guido M, Cillo U, Canova D, Bendinelli M, Pistello M, Maggi F, Palu G (2008) Torque teno virus: any pathological role in liver transplanted patients? Transpl Int 21(10):972–979. doi:10.1111/j.1432-2277.2008.00714.x PubMedCrossRefGoogle Scholar
  8. Carstens EB (2010) Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2009). Arch Virol 155(1):133–146. doi:10.1007/s00705-009-0547-x PubMedCrossRefGoogle Scholar
  9. Chen T, Vaisanen E, Mattila PS, Hedman K, Soderlund-Venermo M (2013) Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays. J Gen Virol 94(Pt 2):409–417. doi:10.1099/vir.0.046862-0 PubMedCrossRefGoogle Scholar
  10. Colonna-Romano G, Akbar AN, Aquino A, Bulati M, Candore G, Lio D, Ammatuna P, Fletcher JM, Caruso C, Pawelec G (2007) Impact of CMV and EBV seropositivity on CD8 T lymphocytes in an old population from West-Sicily. Exp Gerontol 42(10):995–1002. doi:10.1016/j.exger.2007.05.006 PubMedCrossRefGoogle Scholar
  11. Crough T, Khanna R (2009) Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev 22(1):76–98. doi:10.1128/cmr.00034-08 PubMedCrossRefPubMedCentralGoogle Scholar
  12. Focosi D, Maggi F, Albani M, Macera L, Ricci V, Gragnani S, Di Beo S, Ghimenti M, Antonelli G, Bendinelli M, Pistello M, Ceccherini-Nelli L, Petrini M (2010) Torquetenovirus viremia kinetics after autologous stem cell transplantation are predictable and may serve as a surrogate marker of functional immune reconstitution. J Clin Virol 47(2):189–192PubMedCrossRefGoogle Scholar
  13. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128(1):92–105. doi:10.1016/j.mad.2006.11.016 PubMedCrossRefGoogle Scholar
  14. Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiébaut R, Tibshirani RJ, Davis MM (2014) Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci 111(2):869–874. doi:10.1073/pnas.1321060111 PubMedCrossRefPubMedCentralGoogle Scholar
  15. Gameiro CM, Romão F, Castelo-Branco C (2010) Menopause and aging: changes in the immune system—a review. Maturitas 67(4):316–320. doi:10.1016/j.maturitas.2010.08.003 PubMedCrossRefGoogle Scholar
  16. Goronzy JJ, Weyand CM (2013) Understanding immunosenescence to improve responses to vaccines. Nat Immunol 14(5):428–436. doi:10.1038/ni.2588 PubMedCrossRefPubMedCentralGoogle Scholar
  17. Görzer I, Haloschan M, Jaksch P, Klepetko W, Puchhammer-Stöckl E (2014) Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation. J Heart Lung Transpl 33(3):320–323. doi:10.1016/j.healun.2013.12.007 CrossRefGoogle Scholar
  18. Griffiths P (1999) Time to consider the concept of a commensal virus? Rev Med Virol 9(2):73–74. doi:10.1002/(sici)1099-1654(199904/06)9:2<73::aid-rmv254>3.0.co;2-5 PubMedCrossRefGoogle Scholar
  19. Hadrup SR, Strindhall J, Køllgaard T, Seremet T, Johansson B, Pawelec G, Thor Straten P, Wikby A (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 176(4):2645–2653PubMedCrossRefGoogle Scholar
  20. Hecker M, Qiu D, Marquardt K, Bein G, Hackstein H (2004) Continuous cytomegalovirus seroconversion in a large group of healthy blood donors. Vox Sang 86(1):41–44. doi:10.1111/j.0042-9007.2004.00388.x PubMedCrossRefGoogle Scholar
  21. Kim OY, Chae JS, Paik JK, Seo HS, Jang Y, Cavaillon JM, Lee JH (2012) Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women. Age 34(2):415–425. doi:10.1007/s11357-011-9244-2 PubMedCrossRefPubMedCentralGoogle Scholar
  22. Kincaid RP, Burke JM, Cox JC, de Villiers E-M, Sullivan CS (2013) A human torque teno virus encodes a microRNA that inhibits interferon signaling. PLoS Pathog 9(12):e1003818. doi:10.1371/journal.ppat.1003818 PubMedCrossRefPubMedCentralGoogle Scholar
  23. Klein S, Huber S (2010) Sex differences in susceptibility to viral infection. In: Klein SL, Roberts C (eds) Sex hormones and immunity to infection. Springer, Berlin, pp 93–122. doi:10.1007/978-3-642-02155-8_4 CrossRefGoogle Scholar
  24. Klein SL, Roberts C (eds) (2010) Sex hormones and immunity to infection. Springer, Berlin HeidelbergGoogle Scholar
  25. Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology 23(2):64–74. doi:10.1152/physiol.00040.2007 PubMedCrossRefGoogle Scholar
  26. Maggi F, Pistello M, Vatteroni M, Presciuttini S, Marchi S, Isola P, Fornai C, Fagnani S, Andreoli E, Antonelli G, Bendinelli M (2001) Dynamics of persistent TT virus infection, as determined in patients treated with alpha interferon for concomitant hepatitis C virus infection. J Virol 75(24):11999–12004. doi:10.1128/JVI.75.24.11999-12004.2001 PubMedCrossRefPubMedCentralGoogle Scholar
  27. Maggi F, Pifferi M, Fornai C, Andreoli E, Tempestini E, Vatteroni M, Presciuttini S, Marchi S, Pietrobelli A, Boner A, Pistello M, Bendinelli M (2003) TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity. J Virol 77(4):2418–2425PubMedCrossRefPubMedCentralGoogle Scholar
  28. Maggi F, Andreoli E, Lanini L, Fornai C, Vatteroni M, Pistello M, Presciuttini S, Bendinelli M (2005a) Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried. J Clin Microbiol 43(9):4807–4810. doi:10.1128/JCM.43.9.4807-4810.2005 PubMedCrossRefPubMedCentralGoogle Scholar
  29. Maggi F, Tempestini E, Lanini L, Andreoli E, Fornai C, Giannecchini S, Vatteroni M, Pistello M, Marchi S, Ciccorossi P, Specter S, Bendinelli M (2005b) Blood levels of TT virus following immune stimulation with influenza or hepatitis B vaccine. J Med Virol 75(2):358–365. doi:10.1002/jmv.20278 PubMedCrossRefGoogle Scholar
  30. Mekker A, Tchang VS, Haeberli L, Oxenius A, Trkola A, Karrer U (2012) Immune senescence: relative contributions of age and cytomegalovirus infection. PLoS Pathog 8(8):e1002850. doi:10.1371/journal.ppat.1002850 PubMedCrossRefPubMedCentralGoogle Scholar
  31. Moen EM, Sagedal S, Bjoro K, Degre M, Opstad PK, Grinde B (2003) Effect of immune modulation on TT virus (TTV) and TTV-like-mini-virus (TLMV) viremia. J Med Virol 70(1):177–182. doi:10.1002/jmv.10356 PubMedCrossRefGoogle Scholar
  32. Moro-Garcia MA, Alonso-Arias R, Lopez-Vazquez A, Suarez-Garcia FM, Solano-Jaurrieta JJ, Baltar J, Lopez-Larrea C (2012) Relationship between functional ability in older people, immune system status, and intensity of response to CMV. Age 34(2):479–495. doi:10.1007/s11357-011-9240-6 PubMedCrossRefPubMedCentralGoogle Scholar
  33. Naganuma M, Tominaga N, Miyamura T, Soda A, Moriuchi M, Moriuchi H (2008) TT virus prevalence, viral loads and genotypic variability in saliva from healthy Japanese children. Acta Paediatr 97(12):1686–1690. doi:10.1111/j.1651-2227.2008.00962.x PubMedCrossRefGoogle Scholar
  34. Naylor K, Li G, Vallejo AN, Lee W-W, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ (2005) The influence of age on T cell generation and TCR diversity. J Immunol 174(11):7446–7452PubMedCrossRefGoogle Scholar
  35. Niel C, Saback FL, Lampe E (2000) Coinfection with multiple TT virus strains belonging to different genotypes is a common event in healthy Brazilian adults. J Clin Microbiol 38(5):1926–1930PubMedPubMedCentralGoogle Scholar
  36. O’Connor D, Trück J, Lazarus R, Clutterbuck EA, Voysey M, Jeffery K, Pollard AJ (2013) The effect of chronic cytomegalovirus infection on pneumococcal vaccine responses. J Infect Dis. doi:10.1093/infdis/jit673 Google Scholar
  37. Okamoto H (2009) History of discoveries and pathogenicity of TT viruses. Curr Top Microbiol Immunol 331:1–20PubMedGoogle Scholar
  38. Pawelec G, Derhovanessian E (2011) Role of CMV in immune senescence. Virus Res 157(2):175–179. doi:10.1016/j.virusres.2010.09.010 PubMedCrossRefGoogle Scholar
  39. Pawelec G, Larbi A, Derhovanessian E (2010) Senescence of the human immune system. J Comp Pathol 142(Suppl 1):S39–S44. doi:10.1016/j.jcpa.2009.09.005 PubMedCrossRefGoogle Scholar
  40. Pinho-Nascimento CA, Leite JP, Niel C, Diniz-Mendes L (2011) Torque teno virus in fecal samples of patients with gastroenteritis: prevalence, genogroups distribution, and viral load. J Med Virol 83(6):1107–1111. doi:10.1002/jmv.22024 PubMedCrossRefGoogle Scholar
  41. Puchhammer-Stöckl E, Aberle SW, Heinzl H (2012) Association of age and gender with alphaherpesvirus infections of the central nervous system in the immunocompetent host. J Clin Virol 53(4):356–359. doi:10.1016/j.jcv.2011.12.015 PubMedCrossRefGoogle Scholar
  42. Roberts ET, Haan MN, Dowd JB, Aiello AE (2010) Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol 172(4):363–371. doi:10.1093/aje/kwq177 PubMedCrossRefPubMedCentralGoogle Scholar
  43. Rocchi J, Ricci V, Albani M, Lanini L, Andreoli E, Macera L, Pistello M, Ceccherini-Nelli L, Bendinelli M, Maggi F (2009) Torquetenovirus DNA drives proinflammatory cytokines production and secretion by immune cells via toll-like receptor 9. Virology 394(2):235–242. doi:10.1016/j.virol.2009.08.036 PubMedCrossRefGoogle Scholar
  44. Sakiani S, Olsen NJ, Kovacs WJ (2013) Gonadal steroids and humoral immunity. Nat Rev Endocrinol 9(1):56–62PubMedCrossRefGoogle Scholar
  45. Savva GM, Pachnio A, Kaul B, Morgan K, Huppert FA, Brayne C, Moss PAH, The Medical Research Council Cognitive F, Ageing S (2013) Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell 12(3):381–387. doi:10.1111/acel.12059 PubMedCrossRefGoogle Scholar
  46. Shaw AC, Goldstein DR, Montgomery RR (2013) Age-dependent dysregulation of innate immunity. Nat Rev Immunol 13(12):875–887. doi:10.1038/nri3547 PubMedCrossRefPubMedCentralGoogle Scholar
  47. Turner JE, Campbell JP, Edwards KM, Howarth LJ, Pawelec G, Aldred S, Moss P, Drayson MT, Burns VE, Bosch JA (2013) Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults. Age. doi:10.1007/s11357-013-9557-4 PubMedCentralGoogle Scholar
  48. Tyagi AK, Pradier A, Baumer O, Uppugunduri CR, Huezo-Diaz P, Posfay-Barbe KM, Roosnek E, Ansari M (2013) Validation of SYBR Green based quantification assay for the detection of human Torque Teno virus titers from plasma. Virol J 10:191. doi:10.1186/1743-422X-10-1911743-422X-10-191 PubMedCrossRefPubMedCentralGoogle Scholar
  49. Wang GC, Kao WHL, Murakami P, Xue Q-L, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, Fried LP (2010) Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol 171(10):1144–1152. doi:10.1093/aje/kwq062 PubMedCrossRefPubMedCentralGoogle Scholar
  50. Wolf J, Weinberger B, Arnold CR, Maier AB, Westendorp RGJ, Grubeck-Loebenstein B (2012) The effect of chronological age on the inflammatory response of human fibroblasts. Exp Gerontol 47(9):749–753. doi:10.1016/j.exger.2012.07.001 PubMedCrossRefPubMedCentralGoogle Scholar
  51. Zheng H, Ye L, Fang X, Li B, Wang Y, Xiang X, Kong L, Wang W, Zeng Y, Wu Z, She Y, Zhou X (2007) Torque teno virus (SANBAN isolate) ORF2 protein suppresses NF-kappaB pathways via interaction with IkappaB kinases. J Virol 81(21):11917–11924. doi:10.1128/JVI.01101-07 PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© American Aging Association 2014

Authors and Affiliations

  • Mats Haloschan
    • 1
  • Rainer Bettesch
    • 1
  • Irene Görzer
    • 1
  • Lukas Weseslindtner
    • 1
  • Michael Kundi
    • 2
  • Elisabeth Puchhammer-Stöckl
    • 1
  1. 1.Department of VirologyMedical University of ViennaViennaAustria
  2. 2.Institute for Environmental HealthMedical University of ViennaViennaAustria

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