First data on the prevalence of inherited chromosomally integrated Human betaherpesvirus 6A/B in Russia
DOI: https://dx.doi.org/10.18565/epidem.2019.9.4.43-50
Domonova E.A., Silveistrova О.Yu., Goptar I.А., Кuleshov K.V., Nikiforova A.V., Matosova S.V., Shipulina О.Yu.
1) Central Research Institute of Epidemiology, Russian Federal Service for Surveillance of Consumer Rights Protection and Human Well-Being, Moscow, Russia;
2) Academician N.F. Izmerov Research Institute of Occupational Medicine, Moscow, Russia
Objective. To study the prevalence of inherited chromosomally integrated human herpesvirus 6A/B (iciHHV-6A/B) in Russia.
Subjects and methods. A total of 262 apparently healthy people living in Moscow and its Region, as well as 3 members of one family were examined to establish the hereditary transmission of the virus. The investigators used diagnostic and exploratory research techniques, such as real-time PCR, Sanger sequencing, and massively parallel sequencing.
Results. HHV-6A/B DNA was detected in the blood of 5.7% (15/262) cases. The concentrations of HHV-6A/B DNA were <1.0, 1.0–2.0, and >5.0 lg copies/105 cells in 12 (4.6%), 2 (0.8%), and 1 (0.4%) cases, respectively. PCR analysis of the hair follicles and nail plates verified iciHHV-6B status in one examinee. Interpretation of this case established the hereditary transmission in three generations: mother–daughter–grandson. Phylogenomic analysis showed that the Russian clinical endogenous isolates formed a unique monophilic branch within the clade that was represented mainly by iciHHV-6B isolates from Europe.
Conclusion. The investigation provided preliminary data on the detection rate of inherited iciHHV-6A/B in Russia. The prevalence of inherited iciHHV-6B was 0.4% (1/262; 95% CI, 0–2.1); inherited iciHHV-6B was detected and confirmed by laboratory tests in 3 generations. Endogenous iciHHV-6A was not identified. Further large-scale studies are needed in Russia to understand the genetic diversity and geographic stratification of inherited iciHHV-6A and iciHHV-6B.
Literature
- Agut H., Bonnafous P., Gautheret-Dejean A. Update on infections with Human herpesviruses 6A, 6B and 7. Médecine et Maladies Infectieuses 2017; 47(2): 83–91. DOI: 10.1016/j.medmal.2016.09.004
- Arbuckle J.H., Medveczky M.M., Luka J., Hadley S.H., Luegmayr A., Ablashi D., Lund T.C., Tolar J., De Meirleir K., Montoya J.G., Komaroff A.L., Ambros P.F., Medveczky P.G. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc. Natl. Acad. Sci. USA 2010; 107(12): 5563–8. DOI: 10.1073/pnas.0913586107
- Telford M., Navarro A., Santpere G. Whole genome diversity of inherited chromosomally integrated HHV-6 derived from healthy individuals of diverse geographic origin. Sci. Rep. 2018; 8(1): 3472. DOI: 10.1038/s41598-018-21645-x
- Nacheva E.P., Ward K.N., Brazma D., Virgili A., Howard J., Leong H.N., Clark D.A. Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal sites. J. Med. Virol. 2008; 80(11): 1952–8. DOI: 10.1002/jmv.21299
- Gravel А., Hall C., Flamand L. Sequence analysis of transplacentally acquired human herpesvirus 6 DNA is consistent with transmission of a chromosomally integrated reactivated virus. J. Infect. Dis. 2013; 207(10): 1585–9. DOI: 10.1093/infdis/jit060
- Мелехина Е.В., Домонова Э.А., Гоптарь И.А., Шипулина О.Ю., Горелов А.В. Первый в России случай наследственной передачи хромосомно-интегрированного вируса герпеса человека 6В (Human betaherpesvirus 6В). Вопросы практической педиатрии 2019; 14(1): 33–40.Melekhina E.V., Domonova E.A., Goptar I.A., Shipulina O.Yu., Gorelov A.V. [First verified case of hereditary transmission of chromosomally integrated Human betaherpesvirus 6B]. Vorposy praktichenskoy pediatrii 2019; 14(1): 33–40. DOI: 10.20953/1817-7646-2019-1-33-40 (In Russ.).
- Мелехина Е.В., Черкасова С.В., Домонова Э.А., Сильвейстрова О.Ю., Кулешов К.В., Гоптарь И.А., Шипулина О.Ю., Горелов А.В., Чугунова О.Л. Наследуемая хромосомная интеграция Human betaherpesvirus 6B у недоношенных новорожденных. Педиатрия 2019; 98(2): 28–34. Melekhina E.V., Cherkasova S.V., Domonova E.A., Silveystrova O.Yu., Kuleshov K.V., Goptar I.A., Shipulina O.Yu., Gorelov A.V., Chugunova O.L. [Inherited Human betaherpesvirus 6B chromosomal integration in preterm infants]. Pediatria. 2019; 98 (2): 28–34. DOI: 10.24110/0031-403X-2019-98-2-28-34 (In Russ.).
- Flamand L. Chromosomal integration by human herpesviruses 6A and 6B. Adv. Exp. Med. Biol. 2018; 1045: 209–26. DOI: 10.1007/978-981-10-7230-7_10
- Zhang E., Cotton V.E., Hidalgo–Bravo A., Huang Y., Bell A.J., Jarrett R.F., Wilkie G.S., Davison A.J., Nacheva E.P., Siebert R., Majid A., Kelpanides I., Jayne S., Dyer M.J., Royle N.J. HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus-6A from the telomere of chromosome 19q. Sci. Rep. 2016; 6: 22730. DOI: 10.1038/srep22730
- Домонова Э.А., Сильвейстрова О.Ю., Гоптарь И.А., Кулешов К.В., Пасхина И.Н., Никифорова А.В., Шипулина О.Ю., Маркелов М.Л., Шипулин Г.А., Малеев В.В. Первый случай выявления и лабораторного подтверждения наследственной передачи хромосомно-интегрированного Human betaherpesvirus 6А в Российской Федерации. Инфекционные болезни 2019; 17(3): 4–15. DOI: 10.20953/1729-9225-2019-3-5-14Domonova EA, Silveystrova O.Yu., Goptar I.A., Kuleshov K.V., Paskhina I.N., Nikiforova A.V., Shipulina O.Yu., Markelov M.L., Shipulin G.A., Maleev V.V. The first case of detection and laboratory confirmation of the inherited chromosomally integrated Human betaherpesvirus 6A in Russia. Infectious diseases. 2019; 17(3): 4–15. (In Russ.). DOI: 10.20953/1729-9225-2019-3-5-14
- Luppi M., Marasca R., Barozzi P., Ferrari S., Ceccherini–Nelli L., Batoni G., Merelli E., Torelli G. Three cases of human herpesvirus–6 latent infection: integration of viral genome in peripheral blood mononuclear cell DNA. J. Med. Virol. 1993; 40(1): 44–52. DOI: 10.1002/jmv.1890400110
- Daibata M., Taguchi T., Taguchi H., Miyoshi I. Integration of human herpesvirus 6 in a Burkitt’s lymphoma cell line. Br. J. Haematol. 1998; 102(5):1307–13. DOI: 10.1046/j.1365-2141.1998.00903.x
- Morris C., Luppi M., McDonald M., Barozzi P., Torelli G. Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3. J. Med. Virol. 1999; 58(1): 69–75. DOI: 10.1002/(sici)1096-9071(199905)58:1<69::aid-jmv11>3.0.co;2-3
- Pellett P.E., Ablashi D.V., Ambros P.F., Agut H., Caserta M.T., Descamps V., Flamand L., Gautheret–Dejean A., Hall C.B., Kamble R.T., Kuehl U., Lassner D., Lautenschlager I., Loomis K.S., Luppi M., Lusso P., Medveczky P.G., Montoya J.G., Mori Y., Ogata M., Pritchett J.C., Rogez S., Seto E., Ward K.N., Yoshikawa T., Razonable R.R. Chromosomally integrated human herpesvirus 6: questions and answers. Rev. Med. Virol. 2012; 22(3): 144–55. DOI: 10.1002/rmv.715
- Huang Y., Hidalgo–Bravo A., Zhang E., Cotton V.E., Mendez-Bermudez A., Wig G., Medina–Calzada Z., Neumann R., Jeffreys A.J., Winney B., Wilson J.F., Clark D.A., Dyer M.J., Royle N.J. Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome. Nucleic Acids Res. 2014; 42(1): 315–27. DOI: 10.1093/nar/gkt840
- Gravel A., Dubuc I., Morissette G., Sedlak R.H., Jerome K.R., Flamand L. Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris. Proc. Natl. Acad. Sci. USA 2015; 112(26): 8058–63. DOI: 10.1073/pnas.1502741112
- Clark D.A. Clinical and laboratory features of human herpesvirus 6 chromosomal integration. Clin. Microbiol. Infect. 2016; 22(4): 333–9. DOI: 10.1016/j.cmi.2015.12.022
- Leong H.N., Tuke P.W., Tedder R.S., Khanom A.B., Eglin R.P., Atkinson C.E. Atkinson C.E., Ward K.N., Griffiths P.D., Clark D.A. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J. Med. Virol. 2007; 79: 45–51. DOI: 10.1002/jmv.20760
- Hubacek P., Muzikova K., Hrdlickova A., Cinek O., Hyncicova K., Hrstkova H., Sedlacek P., Stary J. Prevalence of HHV-6 integrated chromosomally among children treated for acute lymphoblastic or myeloid leukemia in the Czech Republic. J. Med. Virol. 2009; 81(2): 258–63. DOI: 10.1002/jmv.21371
- Hubacek P., Hrdlickova A., Spacek M., Zajac M., Muzikova K., Sedlacek P, Cetkovsky P. Prevalence of chromosomally integrated HHV-6 in patients with malignant disease and healthy donors in the Czech Republic. Folia Microbiologica 2013; 58(1), 87–90. DOI: 10.1007/s12223-012-0180-z
- Miura H., Kawamura Y., Hattori F., Kozawa K., Ihira M., Ohye T., Kurahashi H., Yoshikawa T. Chromosomally integrated human herpesvirus 6 in the Japanese population. J. Med. Virol. 2018; 90(10): 1636–42. DOI: 10.1002/jmv.25244
- Tanaka-Taya K., Sashihara J., Kurahashi H., Amo K., Miyagawa H., Kondo K., Okada S., Yamanishi K. Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA. J. Med. Virol. 2004; 73(3): 465–73. DOI: 10.1002/jmv.20113
- Hill J.A., HallSedlak R., Magaret A., Huang M.L., Zerr D.M., Jerome K.R., Boeckh M. Efficient identification of inherited chromosomally integrated human herpesvirus 6 using specimen pooling. J. Clin. Virol. 2016; 77: 71–6. DOI: 10.1016/j.jcv.2016.02.016
- Zhang E., Bell A.J., Wilkie G.S., Suárez N.M., Batini C., Veal C.D., Armendáriz–Castillo I., Neumann R., Cotton V.E., Huang Y., Porteous D.J., Jarrett R.F., Davison A.J., Royle N.J. Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact, and potentially able to reactivate from telomeres. J. Virol.; 2017; 91(22): 1137–17. DOI: 10.1128/JVI.01137-17
About the Autors
Elvira A. Domonova, Cand. Biol. Sci., Senior Researcher, Department of Molecular Diagnostics and Epidemiology, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, Moscow, Russia; e-mail: elvira. domonova@pcr.ms; ORCID: http://orcid.org/0000-0001-8262-3938
Olga Y. Silveystrova, Junior Researcher, Department of Molecular Diagnostics and Epidemiology, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, Moscow, Russia; е-mail: olga.silveystrova@pcr.ms; ORCID: https://orcid.org/0000-0001-8412-9765
Irina A. Goptar, Cand. Chem. Sci., Senior Researcher, Laboratory of Postgenomic Technologies, Academician N.F. Izmerov Research Institute of Occupational Medicine, Moscow, Russia; е-mail: probirka@list.ru; ORCID: https://orcid.org/0000-0002-7445-8044
Konstantin V. Kuleshov, Cand. Biol. Sci., Senior Researcher, Department of Molecular Diagnostics and Epidemiology, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, Moscow, Russia; е-mail: konstantinkul@gmail.com; ORCID: http://orcid.org/0000-0002-5238-7900
Anastasia V. Nikiforova, Junior Researcher, Laboratory of Postgenomic Technologies, Academician N.F. Izmerov Research Institute of Occupational Medicine, Moscow, Russia; е-mail: utkina.anastasia@gmail.com; ORCID: http://orcid.org/0000-0001-6279-2101
Svetlana V. Matosova, Junior Researcher, Department of Molecular Diagnostics and Epidemiology, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, Moscow, Russia; e-mail: svetlana.matosova@cmd.su; ОRCID: http://orcid.org/0000-0001-5158-1755
Olga Y. Shipulina, Cand. Sci. Med., Head, Subdivision of Molecular Diagnostic Methods, Department of Molecular Diagnostics and Epidemiology, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, Moscow, Russia; e-mail: olga.shipulinа@pcr.ms; ORCID: https://orcid.org/ 0000-0003-4679-6772
Similar Articles