Prevalence of Epstein-Barr virus, human papillomavirus, cytomegalovirus and herpes simplex virus type 1 in patients with diabetes mellitus type 2 in south-eastern Poland

Autoři: Jakub Dworzański aff001;  Bartłomiej Drop aff002;  Ewa Kliszczewska aff003;  Małgorzata Strycharz-Dudziak aff004;  Małgorzata Polz-Dacewicz aff003
Působiště autorů: Masovian Specialist Hospital, Radom, Poland aff001;  Department of Information Technology and Medical Statistics, Medical University of Lublin, Lublin, Poland aff002;  Department of Virology, Medical University of Lublin, Lublin, Poland aff003;  Chair and Department of Conservative Dentistry with Endodontics, Medical University of Lublin, Lublin, Poland aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0222607


A microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi living in different niches of the human body, which plays an essential role in many metabolic functions. Modifications in the microbiota composition can lead to several diseases, including metabolic disorders. The aim of this study was to analyze the prevalence of four viruses which can cause persistent infections–Epstein-Barr virus (EBV), human papillomavirus (HPV), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) in patients with diabetes mellitus type 2 (DM2). Blood, saliva and oral swabs were collected from all the study participants. The nested-PCR technique was used to detect the viral DNA. DNA of at least one virus was detected in 71.1% of diabetic patients and in 30% of individuals without diabetes. In patients with diabetes EBV DNA was detected the most frequently (25.4%), followed by HPV– 19.1%, HSV– 10.4% and CMV– 5.2%. A higher percentage of EBV+HPV co-infection was found among men (30.8%). EBV DNA was statistically more often detected in patients living in rural areas (53.7%), while HPV (91.5%) and EBV+HPV co-infection (22.2%) prevailed among patients from urban areas. In patients with a DM2 history longer than 10 years viral infection was detected more frequently. The prevalence of EBV, HPV and the EBV+HPV co-infection was significantly higher in diabetic patients than in individuals without diabetes. The frequency of these infections depended on the duration of the disease (DM2).

Klíčová slova:

Co-infections – Cytomegalovirus infection – Epstein-Barr virus – Human papillomavirus infection – Microbiome – Herpes simplex virus – Viral persistence and latency


1. Pascale A, Marchesi N, Marelli C, Coppola A, Luzi L, Govoni S, et al. Microbiota and metabolic diseases. Endocrine. 2018; 61:357–371. doi: 10.1007/s12020-018-1605-5 29721802

2. Glasner ME. Finding enzymes in the gut metagenome. Science. 2017; 355:577–578. doi: 10.1126/science.aam7446 28183934

3. Parker MT. An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery. Yale J Biol Med. 2016; 89:339–351. 27698618

4. Handley SA. The virome: a missing component of biological interaction networks in health and disease. Genome Med. 2016; 8:5. doi: 10.1186/s13073-015-0258-8

5. Houghton D, Hardy T, Stewart C, Errington L, Day CP, Trenell MI, et al. Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes. Diabetologia. 2018; 61:1700–1711. doi: 10.1007/s00125-018-4632-0 29754286

6. Nikolich-Zugich J, Goodrum F, Knox K, Smithey MJ. Known unknowns: how might the persistent herpesvirome shape immunity and aging?. Curr Opin Immunol. 2017; 48:23–30. doi: 10.1016/j.coi.2017.07.011 28780492

7. Carding SR, Davis N, Hoyles L. Review article: the human intestinal virome in health and disease. Aliment Pharmacol Ther 2017; 46:800–815. doi: 10.1111/apt.14280 28869283

8. Han M, Yang P, Zhong C, Ning K. The Human Gut Virome in Hypertension. Front Microbiol. 2018; 9:3150. doi: 10.3389/fmicb.2018.03150 30619215

9. Virgin HW. The virome in mammalian physiology and disease. Cell. 2014; 157:142–150. doi: 10.1016/j.cell.2014.02.032 24679532

10. Boppana SB, Fowler KB. Persistence in the population: epidemiology and transmission. In: Arvin A., Campeadelli-Fiuwe G., editors. Human Herpesviruses: Biology, Therapy and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007. p. 36.

11. Ogilvie LA, Jones BV. The human gut virome: a multifaceted majority. Front Microbiol. 2015; 6:918. doi: 10.3389/fmicb.2015.00918 26441861

12. Casquiero J, Casquiero J, Alves C. Infections in patients with diabete mellitus; A review of pathogenesis. Indian. J Endocrinol Metab. 2012; S27–36. doi: 10.4103/2230-8210.94253 22701840

13. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes. Res Clin Pract. 2017; 128:40–50. doi: 10.1016/j.diabres.2017.03.024 28437734

14. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103:137–49. doi: 10.1016/j.diabres.2013.11.002 24630390

15. Oikonomou E, Mourouzis K, Fountoulakis P, Papamikroulis GA, Siasos G, Antonopoulos A, et al. Interrelationship between diabetes mellitus and heart failure: The role of peroxisome proliferator-activated receptors in left ventricle performance. Heart Fail Rev. 2018; 23:389–408. doi: 10.1007/s10741-018-9682-3 29453696

16. Polz-Dacewicz M, Strycharz-Dudziak M, Dworzanski J, Stec A, Kocot J. Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infection. Infect Agent Cancer. 2016; 11:45. doi: 10.1186/s13027-016-0093-6 27547238

17. Drop B, Strycharz-Dudziak M, Kliszczewska E, Polz-Dacewicz M. Coinfection with Epstein–Barr Virus (EBV), Human Papilloma Virus (HPV) and Polyoma BK Virus (BKPyV) in Laryngeal, Oropharyngeal and Oral Cavity Cancer. Int J Mol Sci. 2017; 18:E2752. doi: 10.3390/ijms18122752 29257122

18. Polz-Gruszka D, Stec A, Dworzański J, Polz-Dacewicz M. EBV, HSV, CMV and HPV an laryngeal and oropharyngeal carcinoma in Polish patients. Anticancer Res. 2015; 35:1657–61. 25750324

19. Cadwell K. The virome in host health and disease. Immunity. 2015; 42:805–813. doi: 10.1016/j.immuni.2015.05.003 25992857

20. Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell. 2009; 138:30–50. doi: 10.1016/j.cell.2009.06.036 19596234

21. Pellett PE, Roizman B. Herpesviridae. In: Knipe DM, Howley P. editors. Fields Virology. Philadelphia:. Wolters Kluwer Health/Lippincott Williams & Wilkins; 2013. p. 1802–22.

22. Looker KJ, Margaret AS, May MT, Turner KME, Vickerman P, Gottlieb SL, et al. Global and Regional Estimates of prevalent and incident Herpes Simplex Virus type 1 infections in 2012. PLoS One. 2015; 10:e0140765. doi: 10.1371/journal.pone.0140765 26510007

23. Needell JC, Zipris D. The role of the intestinal microbiome in type 1 diabetes pathogenesis. Curr Diab Rep. 2016; 16:89. doi: 10.1007/s11892-016-0781-z 27523648

24. Lontchi-Yimagou E, Legoff J, Nguewa JL, Boudou P, Balti EV, Noubiap JJ, et al. Human herpesvirus 8 infection DNA positivity is associated with low insulin secretion: A case-control study in a sub-Saharan African population with diabetes. J Diabetes. 2018; 10:866–873. doi: 10.1111/1753-0407.12777 29707905

25. Zuwala-Jagiello J, Pazgan-Simon M, Murawska-Cialowicz E, Simon K. Influence of diabetes on circulating apoptotic microparticles in patients with chronic hepatitis C. In Vivo. 2017; 31:1027–1034. doi: 10.21873/invivo.11165 28882977

26. Zhang J, Liu YY, Sun HL, Li S, Xiong HR, Yang ZQ, et al. High Human Cytomegalovirus IgG Level is Associated with Increased Incidence of Diabetic Atherosclerosis in Type 2 Diabetes Mellitus Patients. Med Sci Monit. 2015; 21:4102–10. doi: 10.12659/MSM.896071 26717490

27. Giovanuci E, Harlen DM, Archer MC, Bergenstal RM, Gapstur SM, Habel L, et al. Diabetes and cancer. A consensus report. Diabetes Care. 2010; 33:1674–1685. doi: 10.2337/dc10-0666 20587728

28. Yu J. Introduction. In Obesity, Fatty Liver and Liver Cancer. In: Wong CC, Yu J, editors. Advances in Experimental Medicine and Biology, 1061. Singapore, Springer Nature; 2018. p. 1–2.

29. Youn JC, Kim JY, Jung MK, Yu HT, Park SH, Kim IC, et al. Analysis of cytomegalovirus-specific T-cell responses in patients with hypertension: comparison of assay methods and antigens. Clin Hypertens. 2018; 24:5. doi: 10.1186/s40885-018-0090-8 29568571

30. World Health Organization (WHO). Global Report on Diabetes. Geneva: WHO; 2016. doi: 10.2337/db15-0956

31. Karjala Z, Neal D, Rohrer J. Association between HSV-1 seropositivity and obesity: data from the National Health and Nutritional Examination Survey, 2007–2008. PLoS One. 2011; 6:e19092. doi: 10.1371/journal.pone.0019092 21589933

32. Larsen N, Vogensen FK, van den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults. PLoS One. 2010; 5:e9085. doi: 10.1371/journal.pone.0009085 20140211

33. de Jong RGPJ, Peeters PJHL, Burden AM, de Bruin ML, Haak HR, Masclee AAM, et al. Gastrointestinal cancer incidence in type 2 diabetes mellitus; results from a large population-based cohort study in the UK. Cancer Epidemiol. 2018; 54:104–111. doi: 10.1016/j.canep.2018.04.008 29705628

34. Masur K, Vetter C, Hinz A, Tomas N, Henrich H, Niggemann B, et al. Diabetogenic glucose and insulin concentrations modulate transcriptome and protein levels involved in tumour cell migration, adhesion and proliferation. Br J Cancer. 2011; 104:345–52. doi: 10.1038/sj.bjc.6606050 21179032

35. Garg SK, Maurer H, Reed K, Selagamsetty R. Diabetes and cancer: two diseases with obesity as a common risk factor. Diabetes Obes Metab. 2014; 16:97–110. doi: 10.1111/dom.12124 23668396

36. IARC. Monographs on the evaluation of carcinogenic risks to humans A review of human carcinogens. Biological agents. Lyon: World Health Organization; 2012. p.255.

37. Perera RA, Samaranayake LP, Tsang CSP. Shedding dynamics of Epstein-Barr virus: A type 1 carcinogen. Arch Oral Biol. 2010; 55:639–47. doi: 10.1016/j.archoralbio.2010.06.009 20627195

38. Alibek K, Kakpenova A, Baiken Y. Role of infectious agents in the carcinogenesis of brain and head and neck cancers. Infect Agent Cancer. 2013; 8:7–16. doi: 10.1186/1750-9378-8-7 23374258

39. Tsao SW, Tsang CM, Lo KW. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci. 2017; 372:20160270. doi: 10.1098/rstb.2016.0270 28893937

40. Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Cancer Genome Atlas Research Network. Nature. 2014; 513:202–9. doi: 10.1038/nature13480 25079317

41. Garbuglia AR. Human papillomavirus in head and neck cancer. Cancers (Basel). 2014; 6:1705–1726. doi: 10.3390/cancers6031705 25256828

42. Gillison ML, Castellsagué X, Chaturvedi A, Goodman MT, Snijders P, Tommasino M, et al. Eurogin Roadmap: comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix. Int J Cancer. 2014; 134:497–507. doi: 10.1002/ijc.28201 23568556

43. Jalouli J, Jalouli MM, Sapkota D, Ibrahim SO, Larsson PA, Sand L. Human papilloma virus, herpes simplex and Epstein-Barr virus in oral squamous cell carcinoma from eight different countries. Anticancer Res. 2012; 32:571–580. 22287747

44. Syrjänen KJ, Syrjänen SM, Lamberg MA, Pyrhönen S. Human papillomavirus (HPV) involvement in squamous cell lesions of the oral cavity. Proc Finn Dent Soc. 1983; 79:1–8.

Článok vyšiel v časopise


2019 Číslo 9

Najčítanejšie v tomto čísle

Tejto téme sa ďalej venujú…


Zvýšte si kvalifikáciu online z pohodlia domova

Faktory ovlivňující léčbu levotyroxinem
nový kurz

Kurz originály vs. generika

Autori: MUDr. Petr Výborný, CSc., FEBO

Autori: MUDr. Jiří Horažďovský, Ph.D

Klinická farmakokinetika betablokátorů

Všetky kurzy
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.


Nemáte účet?  Registrujte sa