Torque teno virus viral load is related to age, CMV infection and HLA type but not to Alzheimer's disease


Autoři: Gabriel Westman aff001;  Catherine Schoofs aff002;  Martin Ingelsson aff003;  Josef D. Järhult aff001;  Shaman Muradrasoli aff002
Působiště autorů: Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden aff001;  Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden aff002;  Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0227670

Souhrn

Torque teno virus (TTV) is an unenveloped, circular, single stranded DNA virus with a genome size of approximately 3.8 kb. Previous studies have demonstrated varying grades of association between TTV DNA levels and immune deficiencies related to age, chronic infections and cancer. Alzheimer's disease (AD) has been related to persistent viral infections such as HSV-1 and CMV, but it is not known whether TTV viral load could serve as a functional biomarker of cellular immunity in this setting. Therefore, the objective of this study was to investigate whether TTV infection and viral load is related to AD status, CMV immunity, systemic inflammation or HLA types connected to anti-viral immunity. A total of 50 AD subjects and 51 non-demented controls were included in the study. AD subjects were diagnosed according to NINCDS-ADRDA and DSM-IV criteria and neuroradiologic findings were consistent with the diagnosis. TTV viral load was analyzed in plasma samples using a quantitative real-time PCR. Using a cut-off for TTV status at 200 copies/ml, 88% (89/101) of the study subjects were classified as TTV positive. TTV viral load significantly increased with age (beta 0.049 per year, p<0.001) but significantly decreased in relation to CMV IgG levels (beta -0.022 per 1000 units, p = 0.005) and HLA-B27 positivity (beta -0.53, p = 0.023). In conclusion, TTV immune control is not significantly affected by AD status, but appears related to age, CMV humoral immune response and HLA type.

Klíčová slova:

Alzheimer's disease – Anelloviruses – Antiviral immune response – Biomarkers – Cell-mediated immunity – Polymerase chain reaction – Viral load – Viral persistence and latency


Zdroje

1. Itoh Y, Takahashi M, Fukuda M, Shibayama T, Ishikawa T, Tsuda F, et al. Visualization of TT virus particles recovered from the sera and feces of infected humans. Biochemical and biophysical research communications. 2000;279(2):718–24. Epub 2000/12/19. doi: 10.1006/bbrc.2000.4013 11118351.

2. Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M. A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochemical and biophysical research communications. 1997;241(1):92–7. Epub 1998/02/12. doi: 10.1006/bbrc.1997.7765 9405239.

3. Spandole S, Cimponeriu D, Berca LM, Mihaescu G. Human anelloviruses: an update of molecular, epidemiological and clinical aspects. Archives of virology. 2015;160(4):893–908. Epub 2015/02/15. doi: 10.1007/s00705-015-2363-9 25680568.

4. Haloschan M, Bettesch R, Gorzer I, Weseslindtner L, Kundi M, Puchhammer-Stockl E. TTV DNA plasma load and its association with age, gender, and HCMV IgG serostatus in healthy adults. Age (Dordr). 2014;36(5):9716. Epub 2014/10/07. doi: 10.1007/s11357-014-9716-2 25284090; PubMed Central PMCID: PMC4185385.

5. Garcia-Alvarez M, Berenguer J, Alvarez E, Guzman-Fulgencio M, Cosin J, Miralles P, et al. Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with liver disease among patients coinfected with human immunodeficiency virus and hepatitis C virus. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2013;32(2):289–97. Epub 2012/09/18. doi: 10.1007/s10096-012-1744-1 22983402.

6. Fogli M, Torti C, Malacarne F, Fiorentini S, Albani M, Izzo I, et al. Emergence of exhausted B cells in asymptomatic HIV-1-infected patients naïve for HAART is related to reduced immune surveillance. Clin Dev Immunol. 2012;2012:829584. Epub 2012/03/05. doi: 10.1155/2012/829584 22474482; PubMed Central PMCID: PMC3303688.

7. Zhong S, Yeo W, Tang MW, Lin XR, Mo F, Ho WM, et al. Gross elevation of TT virus genome load in the peripheral blood mononuclear cells of cancer patients. Ann N Y Acad Sci. 2001;945:84–92. doi: 10.1111/j.1749-6632.2001.tb03868.x 11708500.

8. Béland K, Dore-Nguyen M, Gagné MJ, Patey N, Brassard J, Alvarez F, et al. Torque Teno virus in children who underwent orthotopic liver transplantation: new insights about a common pathogen. J Infect Dis. 2014;209(2):247–54. Epub 2013/08/06. doi: 10.1093/infdis/jit423 23922368.

9. Gorzer I, Haloschan M, Jaksch P, Klepetko W, Puchhammer-Stockl E. Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2014;33(3):320–3. Epub 2014/02/25. doi: 10.1016/j.healun.2013.12.007 24559947.

10. Focosi D, Maggi F, Albani M, Macera L, Ricci V, Gragnani S, et al. Torquetenovirus viremia kinetics after autologous stem cell transplantation are predictable and may serve as a surrogate marker of functional immune reconstitution. J Clin Virol. 2010;47(2):189–92. doi: 10.1016/j.jcv.2009.11.027 20034850.

11. Giacconi R, Maggi F, Macera L, Pistello M, Provinciali M, Giannecchini S, et al. Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects. Exp Gerontol. 2018;112:103–11. Epub 2018/09/14. doi: 10.1016/j.exger.2018.09.003 30223047.

12. Brassard J, Gagné MJ, Leblanc D, Poitras É, Houde A, Boras VF, et al. Association of age and gender with Torque teno virus detection in stools from diarrheic and non-diarrheic people. J Clin Virol. 2015;72:55–9. Epub 2015/09/02. doi: 10.1016/j.jcv.2015.08.020 26401905.

13. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, et al. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PloS one. 2010;5(3):e9505. Epub 2010/03/09. doi: 10.1371/journal.pone.0009505 20209079; PubMed Central PMCID: PMC2831066.

14. Lovheim H, Olsson J, Weidung B, Johansson A, Eriksson S, Hallmans G, et al. Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer's Disease Development. Journal of Alzheimer's disease: JAD. 2018;61(3):939–45. Epub 2017/12/20. doi: 10.3233/JAD-161305 29254081.

15. Itzhaki RF, Lin W-R, Shang D, Wilcock GK, Faragher B, Jamieson GA. Herpes simplex virus type 1 in brain and risk of Alzheimer's disease. The Lancet. 1997;349(9047):241–4. doi: 10.1016/s0140-6736(96)10149-5

16. Westman G, Berglund D, Widen J, Ingelsson M, Korsgren O, Lannfelt L, et al. Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease. PloS one. 2014;9(5):e96779. Epub 2014/05/09. doi: 10.1371/journal.pone.0096779 24804776; PubMed Central PMCID: PMC4013077.

17. Westman G, Lidehall AK, Magnusson P, Ingelsson M, Kilander L, Lannfelt L, et al. Decreased proportion of cytomegalovirus specific CD8 T-cells but no signs of general immunosenescence in Alzheimer's disease. PloS one. 2013;8(10):e77921. Epub 2013/10/25. doi: 10.1371/journal.pone.0077921 24155977; PubMed Central PMCID: PMC3796487.

18. Kaslow RA, Carrington M, Apple R, Park L, Munoz A, Saah AJ, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nature medicine. 1996;2(4):405–11. Epub 1996/04/01. doi: 10.1038/nm0496-405 8597949.

19. Crux NB, Elahi S. Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections? Frontiers in immunology. 2017;8:832. Epub 2017/08/05. doi: 10.3389/fimmu.2017.00832 28769934; PubMed Central PMCID: PMC5513977.

20. Elahi S, Dinges WL, Lejarcegui N, Laing KJ, Collier AC, Koelle DM, et al. Protective HIV-specific CD8+ T cells evade Treg cell suppression. Nature medicine. 2011;17(8):989–95. Epub 2011/07/19. doi: 10.1038/nm.2422 21765403; PubMed Central PMCID: PMC3324980.

21. Fitzmaurice K, Hurst J, Dring M, Rauch A, McLaren PJ, Gunthard HF, et al. Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection. Gut. 2015;64(5):813–9. Epub 2014/07/06. doi: 10.1136/gutjnl-2013-306287 24996883; PubMed Central PMCID: PMC4392199.

22. Maggi F, Pifferi M, Fornai C, Andreoli E, Tempestini E, Vatteroni M, et al. TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity. Journal of virology. 2003;77(4):2418–25. Epub 2003/01/29. doi: 10.1128/JVI.77.4.2418-2425.2003 12551979; PubMed Central PMCID: PMC141071.

23. Spandole-Dinu S, Cimponeriu DG, Crăciun AM, Radu I, Nica S, Toma M, et al. Prevalence of human anelloviruses in Romanian healthy subjects and patients with common pathologies. BMC Infect Dis. 2018;18(1):334. Epub 2018/07/17. doi: 10.1186/s12879-018-3248-9 30016934; PubMed Central PMCID: PMC6050727.

24. Hsiao KL, Wang LY, Lin CL, Liu HF. New Phylogenetic Groups of Torque Teno Virus Identified in Eastern Taiwan Indigenes. PLoS One. 2016;11(2):e0149901. Epub 2016/02/22. doi: 10.1371/journal.pone.0149901 26901643; PubMed Central PMCID: PMC4762681.

25. Vasilyev EV, Trofimov DY, Tonevitsky AG, Ilinsky VV, Korostin DO, Rebrikov DV. Torque Teno Virus (TTV) distribution in healthy Russian population. Virol J. 2009;6:134. Epub 2009/09/07. doi: 10.1186/1743-422X-6-134 19735552; PubMed Central PMCID: PMC2745379.

26. Borkosky SS, Whitley C, Kopp-Schneider A, zur Hausen H, de Villiers EM. Epstein-Barr virus stimulates torque teno virus replication: a possible relationship to multiple sclerosis. PloS one. 2012;7(2):e32160. Epub 2012/03/03. doi: 10.1371/journal.pone.0032160 22384166; PubMed Central PMCID: PMC3285200.

27. Sherman KE, Rouster SD, Feinberg J. Prevalence and genotypic variability of TTV in HIV-infected patients. Digestive diseases and sciences. 2001;46(11):2401–7. Epub 2001/11/21. doi: 10.1023/a:1012307416122 11713943.


Článok vyšiel v časopise

PLOS One


2020 Číslo 1

Najčítanejšie v tomto čísle

Tejto téme sa ďalej venujú…


Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Význam nutraceutik u kardiovaskulárních onemocnění
nový kurz
Autori:

Faktory ovlivňující léčbu levotyroxinem

Kurz originály vs. generika

Autori: MUDr. Petr Výborný, CSc., FEBO

Autori: MUDr. Jiří Horažďovský, Ph.D

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa