LABORATORY DIAGNOSTICS OF ACTIVE AND LATENT HHV 6-INFECTION IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

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Abstract

Introduction. Human herpes virus type 6 (HHV 6) can cause serious infectious complications in immunodeficient patients. It is also capable of integrating into the genome of the infected cell. Due to this, there can be a misdiagnosis between viral integration and active infection during laboratory diagnostics. Thus, determination of HHV 6 infection using proper laboratory tools is relevant. Also the data on viral interference of HHV 6 and other herpes viruses are very poor especially for patients with hematological malignancies. The aim of the study was to identify laboratory markers of HHV 6 and the form of infection in patients with hematological malignancies. Materials and methods. 98 patients with hematological malignancies positive for HHV 6 DNA during the infectious complication were enrolled in the study. Viral load in leukocytes and plasma of peripheral blood, antiviral M and G immunoglobulins and peripheral blood leukocytes count were evaluated. Results. The majority of patients (66 out of 98, 67.3%) showed laboratory signs of latent HHV 6. Integrated HHV 6 was suspected in 2 patients due to high viral load (1.5x105 copies and 1.7x105 copies), but it was not confirmed subsequently. Additional testing of HCMV and EBV in patients with laboratory signs of active HHV 6 infection revealed the superiority of monoinfection over mixed infection (20 of 32, 62.5%). In cases of mixed infection, the most common co-infectant was HCMV observed in 9 out of 12 (75%) cases. Mild leukopenia accompanied HHV 6 active infection. Conclusion. Laboratory signs of latent HHV 6 tend to be prevalent in patients with hematological malignancies. In patients with laboratory markers of active HHV 6, the monoinfection demonstrated the superiority over mixed one. In cases of mixed infection, HCMV appeared to be the most commonly co-infectant. No cases of an integrated form of HHV 6 have been observed. The viral load of HHV 6 in leukocytes and blood plasma is almost 3 times lower in patients with a mixed infection than with a monoinfection. Active replication of HHV 6 was accompanied with mild leukopenia.

About the authors

N. G. Yaroslavtseva

National Medical Research Center of Hematology

Author for correspondence.
Email: ngyar@yandex.ru
Russian Federation

D. S. Tikhomirov

National Medical Research Center of Hematology

Email: noemail@neicon.ru
Russian Federation

T. Yu. Romanova

National Medical Research Center of Hematology

Email: noemail@neicon.ru
Russian Federation

E. N. Ignatova

National Medical Research Center of Hematology

Email: noemail@neicon.ru
Russian Federation

T. A. Tupoleva

National Medical Research Center of Hematology

Email: noemail@neicon.ru
Russian Federation

F. P. Filatov

National Research Center for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya

Email: noemail@neicon.ru
Russian Federation

T. V. Gaponova

National Medical Research Center of Hematology

Email: noemail@neicon.ru
Russian Federation

References

  1. Pellett P.E., Roizman B. Herpesviridae. In: Knipe D.M., Howley P.M. Fields Virology. Chapter 59. Philadelphia: Lippincott Williams & Wilkins; 2013.
  2. Dominguez G., Dambaugh T.R., Stamey F.R., Dewhurst S., Inoue N., Pellett P.E. Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. J. Virol. 1999; 73(10): 8040-52.
  3. Arbuckle J.H., Pantry S.N., Medveczky M.M., Prichett J., Loomis K.S., Ablashi D., et.al. Mapping the telomere integrated genome of human herpesvirus 6A and 6B. Virology. 2013; 442(1): 3-11.
  4. Yamanishi K., Yasuko M., Pellett P.E. Human Herpesviruses 6 and 7. In: Knipe D.M., Howley P.M. Fields Virology. Chapter 64. Philadelphia: Lippincott Williams & Wilkins; 2013.
  5. Asano Y., Yoshikawa T., Suga S., Yazaki T., Hata T., Nagai T., et al. Viremia and neutralizing antibody response in infants with exanthema subitum. J. Pediatr. 1989; 114(4 Pt. 1): 535-9.
  6. Pellett P.E., Ablashi D.V., Ambros P.F., Agut H., Caserta M.T., Descamps V., et. al. Chromosomally integrated human herpesvirus 6: questions and answers. Rev. Med. Virol. 2012; 22(3): 144-55.
  7. Hall C.B., Caserta M.T., Schnabel K.C., Boettrich C., McDermott M.P., Lofthus G.K., et. al. Dewhurst S. Congenital infections with human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7). J. Pediatr. 2004; 145(4): 472-7.
  8. Ward K.N., Leong H.N., Nacheva E.P., Howard J., Atkinson C.E., Davies N., et.al. Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J. Clin. Microbiol. 2006; 44(4): 1571-4.
  9. Olson A.L., Dahi P.B., Zheng J., Devlin S.V., Lubin M., Gonzales A.M., et.al. Frequent human herpesvirus-6 viremia but low incidence of encephalitis in double-unit cord blood recipients transplanted without antithymocyte globulin. Biol. Blood Marrow Transplant. 2014; 20(6): 787-93.
  10. Razonable R.R. Human herpesvirus 6, 7 and 8 in solid organ transplant recipients. Am. J. Transplant. 2013; 13 (Suppl. 3): 67-78.
  11. Jeulin H., Salmon A., Gautheret-Dejean A., Agut H., Dordigoni P., Fortier B., et.al. Contribution of human herpesvirus 6 (HHV-6) viral load in whole blood and serum to investigate integrated HHV-6 transmission after haematopoietic stem cell transplantation. J. Clin. Virol. 2009; 45(1): 43-6.
  12. Hubacek P., Virgili A., Ward K.N., Pohlreich D., Keslova P., Goldova B., et.al. HHV-6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV-6 and fetal CMV pneumonitis. Br. J. Haematol. 2009; 145(3): 394-8.
  13. Kamble R.T., Clark D.A., Leong H.N., Heslop H.E., Brenner M.K., Carrum G. Transmission of integrated human herpesvirus-6 in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007; 40(6): 563-6.
  14. Leong H.N., Tuke P.W., Tedder R.S., Khanom A.B., Eglin R.P., Atkinson C.E., et.al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J. Med. Virol. 2007; 79(1): 45-51.
  15. Boutolleau D., Agut H., Gautheret-Dejean A. Human herpesvirus 6 genome integration: a possible cause of misdiagnosis of active viral infection? J. Infect. Dis. 2006; 194(7): 1019-20.
  16. Ogata M., Kikuchi H., Satou T., Kawano R., Ikewaki J., Kohno K., et.al. Human herpesvirus 6 DNA in plasma after allogeneic stem cell transplantation: incidence and clinical significance. J. Infect. Dis. 2006; 193(1): 68-79.
  17. De Pagter P.J., Schuurman R., Meijer E., van Baarle D., Sanders E.A., Boelens J.J. Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation. J. Clin. Virol. 2008; 43(4): 361-6.
  18. Boutolleau D., Fernandez C., Andre E., Imbert-Marcille B.M., Milpied N., Agut H., et.al. Human herpesvirus (HHV)-6 and (HHV)-7: two closely related viruses with different infection profile in stem cell transplantation recipients. J. Infect. Dis. 2003; 187(2): 179-86.
  19. Lusso P., Crowley R.W., Malnati M.S., Di Serio C., Ponzoni M., Biancotto A., et.al. Human herpesvirus 6A accelerates AIDS progression in Macaques. Proc. Natl. Acad. Sci. U.S.A. 2007; 104(12): 5067-72.
  20. De Bolle L., Van Loon J., De Clercq E., Naesens L. Quantitative analysis of human herpesvirus 6 cell tropism. J. Med. Virol. 2005; 75(1): 76-85.
  21. McQuaid S., Cosby S.L. An immunohistochemical study of the distribution of the measles virus receptors, CD46 and SLAM in normal human tissues and subacute sclerosing panencephalitis. Lab. Invest. 2002; 82(4): 403-9.
  22. Kondo K., Kondo T., Shimada K., Amo K., Miyagawa H., Yamanishi K. Strong interaction between human herpesvirus 6 and peripheral blood monocytes/macrophages during acute infection. J. Med. Virol. 2002; 67(3): 364-69.
  23. De Bolle L., Naesens L., De Clereq E. Update on human herpesvirus 6 biology, clinical features and therapy. Clin. Microbiol. Rev. 2005; 18(1): 217-45.
  24. Zerr D.M., Meier A.S., Selke S.S., Frenkel L.M., Huang M.L., Wald A., et.al. A population-based study of primary human herpesvirus 6 infection. N. Engl. J. Med. 2005; 352(8): 768-76.
  25. Okuno T., Takahashi K., Balachandra K., Shiraki K., Yamanishi K., Takahashi M., et.al. Seroepidemiology of human herpesvirus 6 infection in normal children and adults. J. Clin. Microbiol. 1989; 27(4): 651-3.
  26. Kawabe S., Ito Y., Ohta R., Sofue A., Gotoh K., Morishima T., et.al. Comparison of the levels of human herpes virus 6 (HHV6) DNA and cytokines in cerebrospinal fluid and serum of children with HHV6 encepalopathy. J. Med. Virol. 2010; 82(8): 1410-5.
  27. Никольский М.А., Радыш М.В. Роль вирусов герпеса человека 6 и 7-го типов в возникновении фебрильных судорог у детей. Вопросы диагностики и педиатрии. 2012; 4(4): 46-8
  28. Yamanishi K., Ocuno T., Shiraki K., Takahashi M., Condo T., Asano Y., et.al. Identification of herpesvirus-6 as a causal agent for exanthema subitum. Lancet. 1988; 1(8594): 1065-7
  29. Львов Н.Д. Герпесвирусы человека - системная, интегративная, лимфопролиферативная иммуноонкопатология. Русский медицинский журнал. 2012; 20(22): 1133-8
  30. Kidd I.M., Clark D.A., Sabin C.A., Andrew D., Hassan-Walker A.F., Sweny P., et.al. Prospective study of human betaherpesviruses after renal transplantation: association of human herpesvirus 7 and cytomegalovirus disease and increased rejection. Transplantation. 2000; 69(11): 2400-4

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Copyright (c) 2018 Yaroslavtseva N.G., Tikhomirov D.S., Romanova T.Y., Ignatova E.N., Tupoleva T.A., Filatov F.P., Gaponova T.V.

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