Genotypic diversity of the varicella-zoster virus (Herpesviridae: Varicellovirus) and human gene variants as risk factors for severe disease

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Abstract

Severe disease progression, including secondary bacterial infections and sepsis, can occur both during initial infection with the varicella-zoster virus (VZV) and its reactivation in the form of herpes zoster. This remains a fairly common problem. However, in most cases, the disease proceeds without complications. In Russia and abroad, varicella is among the most common infectious causes of central nervous system involvement. The most frequent serious complications are skin lesions and associated bacterial infections. The exact causes of these conditions are still not fully understood. Therefore, there is ongoing debate about the possible role of certain viral clades or genetic polymorphisms in patients. This review describes inter-clade differences among viral genotypes, their origins, ability to recombine, clinical cases of infection caused by representatives of different clades, data on their circulation, mechanisms of immune evasion and human candidate genes potentially associated with VZV-related complications. The literature search was conducted using PubMed, Google Scholar, CyberLeninka, and the eLIBRARY.

About the authors

Polina V. Cherkasova

Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency

Email: cherkasovapv@yandex.ru
ORCID iD: 0009-0001-5154-2315

Junior researcher, Department for Experimental Medical Virology, Molecular Genetics and Biobanking

Russian Federation, 197022, St. Petersburg

Aleksandra A. Igolkina

Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency

Email: gribanovaalal@bk.ru
ORCID iD: 0009-0000-4310-9741

Junior researcher, Department for Experimental Medical Virology, Molecular Genetics and Biobanking

Russian Federation, 197022, St. Petersburg

Alina V. Vasilkova

Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency

Email: mock.al@yandex.ru
ORCID iD: 0009-0003-0461-9601

laboratory research assistant, Department for Experimental Medical Virology, Molecular Genetics and Biobanking

Russian Federation, 197022, St. Petersburg

Oleg S. Glotov

Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency

Email: olglotov@mail.ru
ORCID iD: 0000-0002-0091-2224

Doctor of Sciences in Biology, Head of the Department of Experimental Medical Virology, Molecular Genetics and Biobanking

Russian Federation, 197022, St. Petersburg

Olga V. Goleva

Federal Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency

Author for correspondence.
Email: golev.ao@mail.ru
ORCID iD: 0000-0003-3285-9699

PhD, Senior Scientist, Department for Experimental Medical Virology, Molecular Genetics and Biobanking

Russian Federation, 197022, St. Petersburg

References

  1. Shul’zhenko A.E., Shchubelko R.V., Zuikova I.N. Herpesvirus Infections: A Modern Perspective on the Problem [Gerpesvirusnye infektsii: sovremennyi vzglyad na problem]. Moscow: GEOTAR-Media; 2022. https://elibrary.ru/iurmtk (in Russian)
  2. Hope-Simpson R.E. The nature of herpes zoster: a long-term study and a new hypothesis. Proc. R. Soc. Med. 1965; 58(1): 9–20. https://doi.org/10.1177/003591576505800106
  3. Gilden D.H., Vafai A., Shtram Y., Becker Y., Devlin M., Wellish M. Varicella-zoster virus DNA in human sensory ganglia. Nature. 1983; 306(5942): 478–80. https://doi.org/10.1038/306478a0
  4. Zeng T., Lian C.X., Zhang X.Y., Liu P.Q., Ao J., Zhou G.F., et al. Clinical symptoms and molecular epidemiologic characteristics of varicella patients among children and adults in Ganzhou, China. Virol. J. 2025; 22(1): 44. https://doi.org/10.1186/s12985-025-02661-6
  5. Breuer J. The origin and migration of varicella zoster virus strains. J. Infect. Dis. 2019; 221(8): 1213–5. https://doi.org/10.1093/infdis/jiz232
  6. Breuer J., Grose C., Norberg P., Tipples G., Schmid D.S. A proposal for a common nomenclature for viral clades that form the species varicella-zoster virus: summary of VZV Nomenclature Meeting 2008, Barts and the London School of Medicine and Dentistry, 24-25 July 2008. J. Gen. Virol. 2010; 91(Pt. 4): 821–8. https://doi.org/10.1099/vir.0.017814-0
  7. Jensen N.J., Rivailler P., Tseng H.F., Quinlivan M.L., Radford K., Folster J., et al. Revisiting the genotyping scheme for varicella-zoster viruses based on whole-genome comparisons. J. Gen. Virol. 2017; 98(6): 1434–8. https://doi.org/10.1099/jgv.0.000772
  8. Nadtoka M.I., Lysenkov V.G., Agletdinov M.R., Mishkin A.A., Afonina N.M., Ploskireva A.A., et al. Studying the genetic diversity of the varicella-zoster virus in selected regions of the Russian Federation using high-throughput sequencing. Zhurnal mikrobiologii, ehpidemiologii i immunobiologii. 2023; 100(5): 267–75. https://doi.org/10.36233/0372-9311-423 https://elibrary.ru/tkklhp (in Russian)
  9. Arvin A.M., Moffat J.F., Abendroth A., Oliver S.L., eds. Varicella-zoster Virus: Genetics, Pathogenesis and Immunity. Cham: Springer International Publishing; 2023. https://doi.org/10.1007/978-3-031-15305-1
  10. Xu S., Chen M., Zheng H., Wang H., Chen M., Zhou J., et al. Nationwide distribution of varicella-zoster virus clades in China. BMC Infect. Dis. 2016; 16(1): 542. https://doi.org/10.1186/s12879-016-1863-x
  11. Koshizuka T., Ota M., Yamanishi K., Mori Y. Characterization of varicella-zoster virus-encoded ORF0 gene – comparison of parental and vaccine strains. Virology. 2010; 405(2): 280–8. https://doi.org/10.1016/j.virol.2010.06.016
  12. Ramachandran P., Grose C. Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination. Rev. Med. Virol. 2024; 34(3): e2538. https://doi.org/10.1002/rmv.2538
  13. Bryant P., Yildirim T., Griesemer S.B., Shaw K., Ehrbar D., St. George K. Vaccine strain and wild-type clades of varicella-zoster virus in central nervous system and non-CNS disease, New York State, 2004–2019. J. Clin. Microbiol. 2022; 60(4): e02381–21. https://doi.org/10.1128/jcm.02381-21
  14. Shaw J., Halsey N.A., Weinberg A., Scott Schmid D., George K.S., Weldon W.C., et al. Arm paralysis after routine childhood vaccinations: application of advanced molecular methods to the causality assessment of an adverse event after immunization. J. Pediatr. Infect. Dis. Soc. 2017; 6(3): e161–4. https://doi.org/10.1093/jpids/piw084
  15. Pomirchy M., Bommer C., Pradella F., Michalik F., Peters R., Geldsetzer P. Herpes zoster vaccination and dementia occurrence. JAMA. 2025; 333(23): 2083. https://doi.org/10.1001/jama.2025.5013
  16. Norberg P., Depledge D.P., Kundu S., Atkinson C., Brown J., Haque T., et al. Recombination of globally circulating varicella-zoster virus. J. Virol. 2015; 89(14): 7133–46. https://doi.org/10.1128/JVI.00437-15
  17. Peters G.A., Tyler S.D., Grose C., Severini A., Gray M.J., Upton C., et al. A full-genome phylogenetic analysis of varicella-zoster virus reveals a novel origin of replication-based genotyping scheme and evidence of recombination between major circulating clades. J. Virol. 2006; 80(19): 9850–60. https://doi.org/10.1128/JVI.00715-06
  18. Depledge D.P., Gray E.R., Kundu S., Cooray S., Poulsen A., Aaby P., et al. Evolution of cocirculating varicella-zoster virus genotypes during a chickenpox outbreak in Guinea-Bissau. J. Virol. 2014; 88(24): 13936–46. https://doi.org/10.1128/JVI.02337-14
  19. Loparev V., Martro E., Rubtcova E., Rodrigo C., Piette J.C., Caumes E., et al. Toward universal varicella-zoster virus (VZV) genotyping: diversity of VZV strains from France and Spain. J. Clin. Microbiol. 2007; 45(2): 559–63. https://doi.org/10.1128/JCM.01738-06
  20. Jensen N.J., Depledge D.P., Ng T.F.F., Leung J., Quinlivan M., Radford K.W., et al. Analysis of the reiteration regions (R1 to R5) of varicella-zoster virus. Virology. 2020; 546: 38–50. https://doi.org/10.1016/j.virol.2020.03.008
  21. Marra F., Parhar K., Huang B., Vadlamudi N. Risk factors for herpes zoster infection: a meta-analysis. Open Forum Infect. Dis. 2020; 7(1): ofaa005. https://doi.org/10.1093/ofid/ofaa005
  22. Shah H.A., Meiwald A., Perera C., Casabona G., Richmond P., Jamet N. Global prevalence of varicella-associated complications: a systematic review and meta-analysis. Infect. Dis. Ther. 2024; 13(1): 79–103. https://doi.org/10.1007/s40121-023-00899-7
  23. State Report «On the State of Sanitary and Epidemiological Well-Being of the Population in the Russian Federation in 2024». Moscow; 2025. (in Russian)
  24. Sironi M., Peri A.M., Cagliani R., Forni D., Riva S., Biasin M., et al. TLR3 mutations in adult patients with herpes simplex virus and varicella-zoster virus encephalitis. J. Infect. Dis. 2017; 215(9): 1430–4. https://doi.org/10.1093/infdis/jix166
  25. Skripchenko E.Yu., Petrov I.V., Astapova A.V., Klimkin A.V., Skripchenko N.V., Ivanova G.P., et al. Chickenpox and complications in children in modern conditions. Detskie infektsii. 2024; 23(2): 5–9. https://doi.org/10.22627/2072-8107-2024-23-2-5-9 https://elibrary.ru/htqkyz (in Russian)
  26. Matsiyeuskaya N.V., Samoilovich E.O., Semeyko G.V., Gvozdelyuk O.V., Yushkevich A.S. Generalized Varicella Zoster infection in a patient with lymphogranulomatosis after bone marrow transplantation: clinical and laboratory characteristics and virus genotyping. Zhurnal infektologii. 2023; 15(3): 146–51. https://doi.org/10.22625/2072-6732-2023-15-3-146-151 https://elibrary.ru/lydykg (in Russian)
  27. Tome R., Arima S., Akamine M., Hashioka H., Arakaki W., Kami W., et al. Varicella-zoster virus reactivation with severe pneumonia following convalescence from coronavirus disease: A case report and literature review. Intern. Med. 2025; 64(20): 4932–24. https://doi.org/10.2169/internalmedicine.4932-24
  28. González I., Molina-Ortega A., Pérez-Romero P., Echevarría J.E., He L., Tarragó D. Varicella-zoster virus clades circulating in Spain over two decades. J. Clin. Virol. 2019; 110: 17–21. https://doi.org/10.1016/j.jcv.2018.11.008
  29. Depledge D.P., Cudini J., Kundu S., Atkinson C., Brown J.R., Haque T., et al. High viral diversity and mixed infections in cerebral spinal fluid from cases of varicella zoster virus encephalitis. J. Infect. Dis. 2018; 218(10): 1592–601. https://doi.org/10.1093/infdis/jiy358
  30. Howard F.H.N., Kwan A., Winder N., Mughal A., Collado-Rojas C., Muthana M. Understanding immune responses to viruses – do underlying Th1/Th2 cell biases predict outcome? Viruses. 2022; 14(7): 1493. https://doi.org/10.3390/v14071493
  31. Liang F., Glans H., Enoksson S.L., Kolios A.G.A., Loré K., Nilsson J. Recurrent herpes zoster ophthalmicus in a patient with a novel toll-like receptor 3 variant linked to compromised activation capacity in fibroblasts. J. Infect. Dis. 2019; 221(8): 1295–303. https://doi.org/10.1093/infdis/jiz229
  32. Levina A.S., Goleva O.V., Vilnits A.A., Ivanova R.A., Suspitsin E.N., Skripchenko N.V., et al. The role of genetic factors in the development of herpetic encephalitis. A case from practice. Zhurnal infektologii. 2017; 9(4): 153–9. https://doi.org/10.22625/2072-6732-2017-9-4-153-159 (in Russian)
  33. Krivolutskaya T.A., Emelyanova A.N., Emelyanov A.S., Vitkovsky Yu.A. Gene Polymorphism of toll-like receptors in chickenpox patients: observational cohort study. Kubanskii nauchnyi meditsinskii vestnik. 2022; 29(5): 14–28. https://doi.org/10.25207/1608-6228-2022-29-5-14-28 https://elibrary.ru/xbgqmk (in Russian)
  34. Thomsen M.M., Tyrberg T., Skaalum K., Carter-Timofte M., Freytag M.R., Norberg P., et al. Genetic variants and immune responses in a cohort of patients with varicella zoster virus encephalitis. J. Infect. Dis. 2021; 224(12): 2122–32. https://doi.org/10.1093/infdis/jiab254
  35. The GeneCards Suite. In: Practical Guide to Life Science Databases. Singapore: Springer Nature Singapore; 2021: 27–56. https://doi.org/10.1007/978-981-16-5812-9_2
  36. Niemeyer C.S., Frietze S., Coughlan C., Lewis S.W.R., Bustos Lopez S., Saviola A.J., et al. Suppression of the host antiviral response by non-infectious varicella zoster virus extracellular vesicles. J. Virol. 2024; 98(8): e0084824. https://doi.org/10.1128/jvi.00848-24
  37. Sen N., Sommer M., Che X., White K., Ruyechan W.T., Arvin A.M. Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3 (IRF3) phosphorylation at key serine residues: a novel mechanism of IRF3 inhibition among herpesviruses. J. Virol. 2010; 84(18): 9240–53. https://doi.org/10.1128/jvi.01147-10

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Copyright (c) 2025 Cherkasova P.V., Igolkina A.A., Vasilkova A.V., Glotov O.S., Goleva O.V.

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