Herpes virus infection and reproductive health disorders in women. Analytical review

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Abstract

Currently, medicine knows 11,800 types of different viruses (for comparison, until 2011, only 2,800 types of viruses were discovered), which, according to rough estimates by scientists, is no more than 5–10% of all existing viruses on our planet. From 95 to 100% of the population are infected with the herpes virus, and at different periods of life they become infected with at least one, and more often several types of viruses belonging to the herpesvirus family. In the second half of life, almost all people have antibodies to most human herpesviruses. Of the known human herpesviruses, herpes simplex viruses types 1 (HSV-1) and 2 (HSV-2) are the most frequently mentioned in the medical literature, since both of these viruses are associated with lesions of the skin and mucous membranes, commonly known as herpes simplex. However, only recently the role of human herpes viruses (HHVs) as copathogens causing other serious diseases has been recognized. Roseoloviruses are represented by three different types: HHV-6A, -6B, -7, genetically related to cytomegalovirus (CMV). HHVs have broad cellular tropism in vivo and, like other herpesviruses, cause lifelong latent infection in humans. It is known that all known HHVs are found in the reproductive tract. CMV and HHV-6 can contribute to the occurrence of chronic inflammatory diseases of the urogenital tract and impaired fertility in patients. Recent studies have found that HHV-6A is the cause of primary infertility in 43% of cases, and HHV-6A and -6B in some clinical cases contribute to the development of preeclampsia. The role of Epstein–Barr virus (EHV-4), as well as HHV-6, -7 and -8 in the progression of HIV infection is being actively studied. Laboratory diagnosis of HHV-6 and -7 currently has limitations. The most informative method for detecting HHV is the quantitative determination of viral DNA in the blood, other body fluids and organs using real-time polymerase chain reaction. Numerous questions about HHV-6A, -6B and -7 still remain open, particularly regarding the clinical impact and therapeutic options in immunocompromised patients.

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A. A. Khryanin

Novosibirsk State Medical University; Association of Obstetricians-Gynecologists and Dermatovenerologists

Author for correspondence.
Email: khryanin@mail.ru
ORCID iD: 0000-0001-9248-8303

Dr. Sci. (Med.) Professor at the Department of Dermatovenereology and Cosmetology, Novosibirsk State Medical University; President of the Association of Obstetricians-Gynecologists and Dermatovenereologists

Russian Federation, Novosibirsk; Novosibirsk

V. G. Sturov

Novosibirsk National Research State University, V. Zelman Institute for Medicine and Psychology

Email: khryanin@mail.ru
ORCID iD: 0000-0001-8243-247X
Russian Federation, Novosibirsk

References

  1. Yamanishi K., Mori Y., Pellett P.E. Human herpesviruses 6 and 7, p. 2058–2079. Ed. Knipe D.M., Howley P.M., Cohen J.I., Griffin D.E., Lamb R.A., Martin M.A., Racaniello V.R., Roizman B. Fields Virology, 2013; 6th ed, vol. 2. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, PA.
  2. Agut H., Bonnafaus P., Gautheret-Dejean A. Human Herpesviruses 6A, 6B, and 7. Microbiol Spectr. 2016;4(3). doi: 10.1128/microbiolspec.DMIH2-0007-2015.
  3. Salahuddin S.Z., Ablashi D.V., Markham P.D., et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986;234:596–601. doi: 10.1126/science.2876520.
  4. Alazzam M.B., Al-Radaideh A.T., Binsaif N., et al. Advanced Deep Learning Human Herpes Virus 6 (HHV-6) Molecular Detection in Understanding Human Infertility. Comput Intell Neurosci. 2022;2022:1422963.
  5. Agut H., Bonnafous P., Gautheret-Dejean A. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin Microbiol Rev. 2015;28(2):313–35. doi: 10.1128/CMR.00122-14.
  6. Komaroff A.L., Pellett P.E., Jacobson S. Human herpesviruses 6A and 6B in brain diseases: Association vs. causation. Clin Microbiol Rev. 2021;34(1):e00143–20. doi: 10.1128/CMR.00143-20.
  7. Harberts E., Yao K., Wohler J.E., et al. Human herpesvirus-6 entry into the central nervous system through the olfactory pathway. Proc Natl Acad Sci USA. 2011;108(33):13734–39. doi: 10.1073/pnas.1105143108.
  8. Kaufer B.B., Flamand L. Chromosomally integrated HHV-6: impact on virus, cell and organismal biology. Curr Opin Virol. 2014;9:111–18.
  9. Becerra A., Gibson L., Stern L.J., Calvo-Calle J.M. Immune response to HHV-6 and implications for immunotherapy. Curr Opin Virol. 2014; 9C:154–61.
  10. Aswad A., Aimola G., Wight D., et al. Evolutionary history of endogenous human herpesvirus 6 reflects humanmigration out of Africa. Mol Biol Evol. 2020;38:96–107.
  11. Arbuckle J.H., Medveczky M.M., Luka J., et al. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci USA. 2010;107:5563–68.
  12. Komaroff A.L., Rizzo R., Eckler J.L. Human Herpesviruses 6A and 6B in Reproductive Diseases. Front Immunol. 2021;25(12):648945.
  13. Tesini B.L., Epstein L.G., Caserta M.T. Clinical impact of primary infection with roseoloviruses. Curr Opin Virol. 2014;9C:91–96.
  14. Miura H., Kawamura Y., Ohye T., et al. Inherited Chromosomally Integrated Human Herpesvirus 6 Is a Risk Factor for Spontaneous Abortion. J Infect Dis. 2021;223(10):1717–23.
  15. Hall C.B., Caserta M.T., Schnabel K.C., et al. Transplacental congenital human herpesvirus 6 infection caused by maternal chromosomally integrated virus. J Infect Dis. 2010;201:505–7.
  16. Fule Robles J.D., Cheuk D.K., Ha S.Y., et al. Human herpesvirus types 6 and 7 infection in pediatric hematopoietic stem cell transplant recipients. Ann Transplant. 2014;19:269–76.
  17. Sharma A.N., Shwe S., Ravi V., et al. Characterizing DRESS syndrome recurrence: a systematic review. Arch Dermatol Res. 2022;314(8):721–28.
  18. Yoshikawa T. HHV-6B and HHV-7 in exanthema subitum and related skin diseases, p 153–66. Ed. Flamand L., Lautenschlager I., Krueger G., Ablashi D. Human Herpesviruses HHV-6A, HHV-6B & HHV-7, Third Edition. 2014. Elsevier, Amsterdam.
  19. Hama N., Abe R., Gibson A., Phillips E.J. Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis. J Allergy Clin Immunol Pract. 2022;10(5):1155–1167.e5.
  20. Mardivirin L., Valeyrie-Allanore L., Branlant-Redon E., et al. Amoxicillin-induced flare in patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): report of seven cases and demonstration of a direct effect of amoxicillin on human herpesvirus 6 replication in vitro. Eur J Dermatol. 2010;20:68–73.
  21. Bezerra T.M., Ferreira D.C., Carmo F.L., et al. Herpesvirus in the oral cavity of children with leukaemia and its impact on the oral bacterial community profile. J Clin Pathol. 2015; 68:222–28.
  22. Drago F., Javor S., Bruzzone L., et al. Pityriasis rosea in a hepatitis B-positive patient treated with pegylated interferon α2a: report of a case and review of the literature. Dermatology. 2014;228:10–13.
  23. Yao K., Crawford J.R., Komaroff A.L., et al. Review part 2: human herpesvirus-6 in central nervous system diseases. J Med Virol. 2010; 82:1669–78.
  24. Virtanen J.O., Pietilдinen-Nicklйn J., Uotila L., et al. Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid. J Neuroimmunol. 2011;237:93–7.
  25. Caselli E., Boni M., Bracci A., et al. Detection of antibodies directed against human herpesvirus 6 U94/REP in sera of patients affected by multiple sclerosis. J Clin Microbiol. 2002;40:4131–37.
  26. Broccolo F. HHV-6A and HHV-6B in autoimmune disease, p 167–78. E. Flamand L., Lautenschlager I., Krueger G., Ablashi D. Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. 2014. Elsevier, New York, NY.
  27. Caselli E., Zatelli M.C., Rizzo R., et al. Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto’s thyroiditis. PLoS Pathog. 2012;8:e1002951.
  28. Zerr D.M., Komaroff A.L. Cognitive dysfunction from HHV-6A and HHV-B, p. 99-122. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. 2014. Elsevier, New York, NY.
  29. Ariza M.E. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! Biomolecules. 2021;11(2):185.
  30. Maltsev D. A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV-6 and HHV-7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis. Microbiol. Immunol. 2022;66(4):193–99.
  31. Barratt C.L.R., Wang C., Baldi E., et al. What advances may the future bring to the diagnosis, treatment, and care of male sexual and reproductive health? Editorial Board Members of the WHO Laboratory Manual for the Examination and Processing of Human Semen. Fertil Steril. 2022;117(2):258–67.
  32. Ковалык В.П., Владимирова Е.В., Колиева Г.Л. и др. Цитомегаловирус, вирус Эпштейна-Барр и вирус герпеса 6 типа в качестве инфекций, передаваемых половым путем: обзор литературы. Современные проблемы здравоохранения и медицинской статистики. 2023;2:50–65. [Kovalyk V.P., [Vladimirova E.V., Kolieva G.L., et al. Cytomegalovirus, Epstein-Barr virus, and herpes virus type 6 as sexually transmitted infections: a literature review.Sovremennye problemy zdravookhraneniya i meditsinskoi statistiki. 2023;2:50–65. (In Russ.)].
  33. Кущ А.А., Кистенёва Л.Б., Климова Р.Р., Чешик С.Г. Роль герпесвирусов в развитии заболеваний урогенитального тракта и бесплодия у женщин. Вопросы вирусологии. 2020;65(6):317–25. [Kushch A.A., Kisteneva L.B., Klimova R.R., Cheshik S.G. The role of herpesviruses in the development of urogenital tract diseases and infertility in women. Voprosy virusologii. 2020;65(6):317–25. (In Russ.)].
  34. Bortolotti D., Soffritti I., D’Accolti M., et al. HHV-6A Infection of Endometrial Epithelial Cells Affects miRNA Expression and Trophoblast Cell Attachment. Reprod Sci. 2020;27(3):779–86.
  35. Coulam C.B., Bilal M., Salazar Garcia M.D., et al. Prevalence of HHV-6 in endometrium from women with recurrent implantation failure. Am J Reprod Immunol. 2018;80(1):e12862.
  36. Schwartz K.L., Richardson S.E., Ward K.N., et al. Delayed primary HHV-7 infection and neurologic disease. Pediatrics. 2014;133:e1541–47.
  37. Wight D.J., Aimola G., Aswad A., et al. Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6. Proc Natl Acad Sci USA. 2020;117(49):31410–16. doi: 10.1073/pnas.2011872117.
  38. Gaccioli F., Lager S., de Goffau M.C., et al. Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia. Nat Microbiol. 2020;5(7):901–8.
  39. Miura H., Kawamura Y., Ohye T., et al. Inherited chromosomally integrated human herpesvirus 6 is a risk factor for spontaneous abortion. J Infect Dis. 2020;132:104656.
  40. Farsimadan M., Motamedifar M. The effects of human immunodeficiency virus, human papillomavirus, herpes simplex virus-1 and -2, human herpesvirus-6 and -8, cytomegalovirus, and hepatitis B and C virus on female fertility and pregnancy. Br J Biomed Sci. 2021;78(1):1–11.
  41. Epstein L.G., Shinnar S., Hesdorffer D.C., et al. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia. 2012;53:1481–88.
  42. Caserta M.T., Hall C.B., Canfield R.L., et al. Early developmental outcomes of children with congenital HHV-6 infection. Pediatrics. 2014;134:1111–18.
  43. Clark D.A., Griffiths P.D. Human herpesvirus 6: relevance of infection in the immunocompromised host. Br J Haematol. 2003;120:384–95.
  44. Ogata M., Satou T., Kadota J., et al. Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study. Clin Infect Dis. 2013;57:671–81.
  45. Bortolotti D., Gentili V., Caselli E., et al. DNA sensors’ signaling in NK cells during HHV-6A, HHV-6B and HHV-7 infection. Front Microbiol. 2020;11:226.
  46. Marci R., Gentili V., Bortolotti D., et al. Presence of HHV-6A in endometrial epithelial cells from women with primary unexplained infertility. PloS One. 2016;11(7):e0158304.
  47. Lessey B.A., Young S.L. What exactly is endometrial receptivity? Fertil Steril. 2019;111(4):611–7.
  48. Lautenschlager I., Razonable R.R. HHV-6A and HHV-6B in solid organ transplantation, p 201–215. Ed. Flamand L., Lautenschlager I., Krueger G., Ablashi D. Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. 2014. Elsevier, New York, NY.
  49. Razonable R.R. Infections due to human herpesvirus 6 in solid organ transplant recipients. Curr Opin Organ Transplant. 2010;15:671–75.
  50. Shmeleva E.V., Colucci F. Maternal natural killer cells at the intersection between reproduction and mucosal immunity. Mucosal Immunol. 2021;14(5):991–1005.
  51. Chaiworapongsa T., Chaemsaithong P., Yeo L., Romero R. Preeclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol. 2014;10(8):466–80. doi: 10.1038/nrneph.2014.102.
  52. Клинические рекомендации «Аногенитальная герпетическая вирусная инфекция», 2021. (Электронный ресурс). URL: https://cr.minzdrav.gov.ru/schema/679_1 (дата обращения: 05.07.2024). [Clinical guidelines «Anogenital herpes viral infection», 2021. (Electronic resource). URL: https://cr.minzdrav.gov.ru/schema/679_1 (date of access: 07/05/2024). (In Russ.)].
  53. Халдин А.А., Полеско И.В., Парфенов В.В. Регламент ведения пациентов с простым герпесом и тактика купирования обострений инфекции. Клиническая дерматология и венерология. 2020;19(3):407–10. [Khaldin A.A., Polesko I.V., Parfenov V.V. Regulations for the management of patients with herpes simplex and tactics for stopping exacerbations of infection. Klinicheskaya dermatologiya i venerologiya. 2020;19(3):407–10. (In Russ.)].
  54. Хрянин А.А., Кнорринг Г.Ю., Соколовская А.В. Интерферонотерапия рецидивирующей герпесвирусной инфекции. Клиническая дерматология и венерология. 2022;21(2):214–19. [Khryanin A.A., Knorring G.Yu., Sokolovskaya A.V. Interferon therapy for recurrent herpesvirus infection. Klinicheskaya dermatologiya i venerologiya. 2022;21(2):214–19. (In Russ.)].
  55. Pritchett J.C., Naesens L., Montoya J. Treating HHV-6 infections: the laboratory efficacy and clinical use of anti-HHV-6 agents, p. 311–31. Ed. Flamand L., Lautenschlager I., Krueger G., Ablashi D. Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. 2014. Elsevier, New York, NY.
  56. Prichard M.N., Whitley R.J. The development of new therapies for human herpesvirus 6. Curr Opin Virol. 2014;9:148–53.
  57. De Clercq E., Naesens L., De Bolle L., et al. Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8. Rev Med Virol. 2001;11:381–95.
  58. Гизингер О.А. Клинико-лабораторное обоснование и оценка эффективности рекомбинантного интерферона α-2b в терапии генитального герпеса. Инфекционные болезни. 2021;19(3):58–66. [Gizinger O.A. Clinical and laboratory justification and evaluation of the efficacy of recombinant interferon α-2b in the treatment of genital herpes. Infektsionnye bolezni. 2021;19(3):58–66. (In Russ.)]. doi: 10.20953/1729-9225-2021-3-58-66.
  59. Васильев А.Н., Каграманова Ж.А., Малиновская В.В., Парфенов В.В. Препарат Виферон, суппозитории, в терапии рецидивирующей герпесвирусной инфекции у женщин. Антибиотики и Химиотерапия. 2009;54(5-6):54–58. [Vasiliev A.N., Kagramanova Zh.A., Malinovskaya V.V., Parfenov V.V. The drug Viferon, suppositories, in the treatment of recurrent herpesvirus infection in women. Antibiotiki i Khimioterapiya. 2009;54(5-6):54–58. (In Russ.)].
  60. Игнатьев Д.В. Роль препарата Виферон® в терапии простого герпеса. Эффективная фармакотерапия. 2012;30:24–27. [Ignat’ev D.V. The role of the drug Viferon® in the treatment of herpes simplex. Effektivnaya farmakoterapiya. 2012;30:24–27. (In Russ.)].
  61. Халдин А.А., Чистик О.В., Игнатьев Д.В., Васильев А.Н. Новые аспекты в терапии простого герпеса. Дерматология. Приложение к журналу Consilium Medicum. 2009;2:21–27. [Khaldin A.A., Chistik O.V., Ignat’ev D.V., Vasiliev A.N. New aspects in the therapy of herpes simplex. Dermatologiya (supp). Consilium Medicum. 2009;2:21–27. (In Russ.)].
  62. Рищук С.В., Кахиани Е.И., Мирский В.Е. и др. Перспективы использования интерферона в лечении бесплодия у мужчин. Лечащий врач. 2018;4:75–85. [Rishchuk S.V., Kakhiani E.I., Mirskii V.E., et al. Prospects for the use of interferon in the treatment of male infertility. Lechashchii vrach. 2018;4:75–85. (In Russ.)].
  63. Kapranos N, Petrakou E, Anastasiadou C, Kotronias D. Detection of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus in the semen of men attending an infertility clinic. Fertil Steril. 2003;79 Suppl 3:1566–70.
  64. Ковалык В.П., Гомберг М.А., Брагина Е.Е. и др. Роль герпесвирусов при мужском бесплодии. Русский медицинский журнал. Медицинское обозрение. 2021;5(3):123–29. [Kovalyk V.P., Gomberg M.A., Bragina E.E. et al. he role of herpesviruses in male infertility. Russkii meditsinskii zhurnal. Meditsinskoe obozrenie. 2021;5(3):123–29. (In Russ.)]. doi: 10.32364/2587-6821-2021-5-3-123-129.
  65. Pollack B, von Saltza E, McCorkell L, et al. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Front Rehabil Sci. 2023;4:1122673.
  66. Нестерова И.В., Балмасова И.П. Интерфероно- и иммунотерапия в реабилитации пациентов с постинфекционным синдромом хронической усталости и иммунной дисфункции. Учебно-методическое пособие. М.: Capricorn Publishing, 2012. 26 с. [Nesterova I.V., Balmasova I.P. Interferon and immunotherapy in the rehabilitation of patients with post-infectious chronic fatigue syndrome and immune dysfunction. Tutorial. Moscow: Capricorn Publishing, 2012. 26 p. (In Russ.)].
  67. Нестерова И.В., Халтурина Е.О., Малиновская В.В. Клинико-иммунологическая эффективность интеграционной программы реабилитации иммунной системы у пациентов с атипичной хронической активной герпесвирусной коинфекцией до и во время COVID-19, а также в постковидном периоде. Эффективная фармакотерапия. 2022;18 (37):30–41. [Nesterova I.V., Khalturina E.O., Malinovskaya V.V. Clinical and immunological effectiveness of the integrated program for the rehabilitation of the immune system in patients with atypical chronic active herpesvirus coinfection before and during COVID-19, as well as in the post-COVID period. Effektivnaya farmakoterapiya. 2022;18 (37):30–41. (In Russ.)].

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