Skip to main content
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;11(4):475–479. doi: 10.1111/j.1750-3639.2001.tb00416.x

An Animal Model of Varicella Virus Infection

Tiffany M White 1,2, Donald H Gilden 1,2, Ravi Mahalingam 1,
PMCID: PMC8098339  PMID: 11556693

Abstract

Varicella‐zoster virus (VZV) causes chickenpox in children; establishes latency in cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later to produce zoster. VZV produces disease only in humans. Although attempts to produce disease and study VZV latency in experimentally infected animals have resulted in virus in trigeminal or dorsal root ganglia, no clinical signs of infection or reactivation developed. In contrast, simian varicella virus (SVV) produces a naturally occurring exanthematous disease in non‐human primates that mimics human varicella. Experimental inoculation of non‐human primates causes similar, if not identical, clinical and pathological changes observed in monkeys naturally infected with SVV. Like VZV, SVV becomes latent in ganglia and reactivates, often with entire body rash. SVV and VZV encode antigenically related polypeptides. Both virus genomes have been sequenced and shown to be colinear, sharing up to 75% DNA homology. During latency, an SVV homolog of one of the five VZV genes transcribed in latently infected human ganglia has been detected in monkey ganglia. Preliminary studies in which monkeys were inoculated intratracheally with SVV revealed the presence of viral DNA and RNA in multiple tissues, including blood mononuclear cells, months after experimental infection. These findings differed from the expected restricted localization of the virus DNA to ganglia only and the expected limited viral gene expression, and probably reflect the high virus load delivered intratracheally compared to natural SVV infection in monkeys. Nevertheless, clinical, pathological, and molecular similarities between SVV and VZV indicate that SVV infection in non‐human primates has considerable potential as an animal model for human varicella.

Full Text

The Full Text of this article is available as a PDF (26.6 KB).

References

  • 1. Annunziato P, LaRussa P, Lee P, Steinberg S, Lungu O, Gershon AA, Silverstein S (1998) Evidence of latent varicella‐zoster virus in rat dorsal root ganglia. J Infect Dis 178 (Suppl 1): S48–S51. [DOI] [PubMed] [Google Scholar]
  • 2. Clarke P, Matlock WL, Beer T, Gilden DH (1996) A simian varicella virus (SVV) homolog to varicella‐zoster virus gene 21 is expressed in monkey ganglia latently infected with SVV. J Virol 70: 5711–5715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Clarke P, Rabkin SD, Inman MV, Mahalingam R, Cohrs R, Wellish M, Gilden DH (1992) Molecular analysis of simian varicella virus DNA. Virology 190: 597–605. [DOI] [PubMed] [Google Scholar]
  • 4. Clarkson MJ, Thorpe E, McCarthy K (1967) A virus disease of captive vervet monkeys (Cercopithecus aethiops) caused by a new herpesvirus. Arch Gesamte Virusforsch 22: 219–234. [DOI] [PubMed] [Google Scholar]
  • 5. Cohen JI, Moskal T, Shapiro M, Purcell RH (1996) Varicella in chimpanzees. J Med Virol 50: 289–292. [DOI] [PubMed] [Google Scholar]
  • 6. Davison AJ, Scott JE (1986) The complete DNA sequence of varicella‐zoster virus. J Gen Virol 67: 1759–1816. [DOI] [PubMed] [Google Scholar]
  • 7. Debrus S, Sadzot‐Delvaux C, Nikkels AF, Piette J, Rentier B (1995) Varicella‐zoster virus gene 63 encodes an immediate‐early protein that is abundantly expressed during latency. J Virol 69: 3240–3245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Dueland AN, Martin JR, Devlin ME, Wellish M, Mahalingam R, Cohrs R, Soike KF, Gilden DH (1992) Acute simian varicella infection. Clinical, laboratory, pathologic, and virologic features. Lab Invest 66: 762–773. [PubMed] [Google Scholar]
  • 9. Felsenfeld AD, Schmidt NJ (1979) Varicella‐zoster virus immunizes patas monkeys against simian varicella‐like disease. J Gen Virol 42: 171–178. [DOI] [PubMed] [Google Scholar]
  • 10. Fletcher TM, Gray WL (1992) Simian varicella virus: characterization of virion and infected cell polypeptides and the antigenic cross‐reactivity with varicella‐zoster virus. J Gen Virol 73: 1209–1215. [DOI] [PubMed] [Google Scholar]
  • 11. Gilden DH, Gesser R, Smith J, Wellish M, LaGuardia JJ, Cohrs RJ, Mahalingam R (2001) Presence of VZV and HSV‐1 DNA in human nodose and celiac ganglia. Virus Genes in press. [DOI] [PubMed] [Google Scholar]
  • 12. Gray WL, Oakes JE (1984) Simian varicella virus DNA shares homology with human varicella‐zoster virus DNA. Virology 136: 241–246. [DOI] [PubMed] [Google Scholar]
  • 13. Gray WL, Pumphrey CY, Ruyechan WT, Fletcher TM (1992) The simian varicella virus and varicella‐zoster virus genomes are similar in size and structure. Virology 186: 562–572. [DOI] [PubMed] [Google Scholar]
  • 14. Gray WL, Starnes B, White MW, Mahalingam R (2001) The DNA sequence of the simian varicella virus genome. Virology 284: 123–130. [DOI] [PubMed] [Google Scholar]
  • 15. Harnisch JP (1984) Zoster in the elderly: clinical, immunologic and therapeutic considerations. J Am Geriatr Soc 32: 789–793. [DOI] [PubMed] [Google Scholar]
  • 16. Iltis JP, Arrons MC, Castellano GA, Madden DL, Sever JL, Curfman BL, London WT (1982) Simian varicella virus (delta herpesvirus) infection of patas monkeys leading to pneumonia and encephalitis. Proc Soc Exp Biol Med 169: 266–279. [DOI] [PubMed] [Google Scholar]
  • 17. Mahalingam R, Clarke P, Wellish M, Dueland AN, Soike KF, Gilden DH, Cohrs R (1992) Prevalence and distribution of latent simian varicella virus DNA in monkey ganglia. Virology 188: 193–197. [DOI] [PubMed] [Google Scholar]
  • 18. Mahalingam R, Smith D, Wellish M, Wolf W, Dueland AN, Cohrs R, Soike K, Gilden D (1991) Simian varicella virus DNA in dorsal root ganglia. Proc Natl Acad Sci USA 88: 2750–2752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Mahalingam R, Wellish M, Soike K, White T, Kleinschmidt‐DeMasters BK, Gilden DH (2001) Simian varicella virus infects ganglia before rash in experimentally infected monkeys. Virology 279: 339–342. [DOI] [PubMed] [Google Scholar]
  • 20. Mahalingam R, Wellish M, Wolf W, Dueland AN, Cohrs R, Vafai A, Gilden D (1990) Latent varicella‐zoster viral DNA in human trigeminal and thoracic ganglia. N Engl J Med 323: 627–631. [DOI] [PubMed] [Google Scholar]
  • 21. Mahalingam R, White T, Wellish M, Gilden DH, Soike K, Gray WL (2000) Sequence analysis of the leftward end of simian varicella virus (EcoRI‐I fragment) reveals the presence of an 8‐bp repeat flanking the unique long segment and an 881‐bp open‐reading frame that is absent in the varicella‐zoster virus genome. Virology 274: 420–428. [DOI] [PubMed] [Google Scholar]
  • 22. Matsunaga Y, Yamanishi K, Takahashi M (1982) Experimental infection and immune response of guinea pigs with varicella‐zoster virus. Infect Immun 37: 407–412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Merville‐Louis MP, Sadzot‐Delvaux C, Delree P, Piette J, Moonen G, Rentier B (1989) Varicella‐zoster virus infection of adult rat sensory neurons in vitro. J Virol 63: 3155–3160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Moffat JF, Stein MD, Kaneshima H, Arvin AM (1995) Tropism of varicella‐zoster virus for human CD4+ and CD8+ T lymphocytes and epidermal cells in SCID‐hu mice. J Virol 69: 5236–5242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Myers MG, Connelly BL (1992) Animal models of varicella. J Infect Dis 166 (Suppl 1): S48–S50. [DOI] [PubMed] [Google Scholar]
  • 26. Myers MG, Duer HL, Hausler CK (1980) Experimental infection of guinea pigs with varicella‐zoster virus. J Infect Dis 142: 414–420. [DOI] [PubMed] [Google Scholar]
  • 27. Myers MG, Stanberry LR, Edmond BJ (1985) Varicella‐zoster virus infection of strain 2 guinea pigs. J Infect Dis 151: 106–113. [DOI] [PubMed] [Google Scholar]
  • 28. Padovan D, Cantrell CA (1986) Varicella‐like herpesvirus infections of nonhuman primates. Lab Anim Sci 36: 7–13. [PubMed] [Google Scholar]
  • 29. Pavan‐Langston D, Dunkel EC (1989) Ocular varicella‐zoster virus infection in the guinea pig. A new in vivo model. Arch Ophthalmol 107: 1068–1072. [DOI] [PubMed] [Google Scholar]
  • 30. Pumphrey CY, Gray WL (1992) The genomes of simian varicella virus and varicella‐zoster virus are colinear. Virus Res 26: 255–266. [DOI] [PubMed] [Google Scholar]
  • 31. Roberts ED, Baskin GB, Soike K, Gibson SV (1984) Pathologic changes of experimental simian varicella (Delta herpesvirus) infection in African green monkeys (Cercopithecus aethiops). Am J Vet Res 45: 523–530. [PubMed] [Google Scholar]
  • 32. Roberts RB, Murray HW, Rubin BY, Masur H (1983) Opportunistic infections and impaired cell‐mediated immune responses in patients with the acquired immune deficiency syndrome. Trans Am Clin Climatol Assoc 95: 40–51. [PMC free article] [PubMed] [Google Scholar]
  • 33. Sadzot‐Delvaux C, Merville‐Louis MP, Delree P, Marc P, Piette J, Moonen G, Rentier B (1990) An in vivo model of varicella‐zoster virus latent infection of dorsal root ganglia. J Neurosci Res 26: 83–89. [DOI] [PubMed] [Google Scholar]
  • 34. Soike KF (1992) Simian varicella virus infection in African and Asian monkeys. The potential for development of antivirals for animal diseases. Ann NYAcad Sci 653: 323–333. [DOI] [PubMed] [Google Scholar]
  • 35. Soike KF, Keller PM, Ellis RW (1987) Immunization of monkeys with varicella‐zoster virus glycoprotein antigens and their response to challenge with simian varicella virus. J Med Virol 22: 307–313. [DOI] [PubMed] [Google Scholar]
  • 36. Soike KF, Rangan SR, Gerone PJ (1984) Viral disease models in primates. Adv Vet Sci Comp Med 28: 151–199. [DOI] [PubMed] [Google Scholar]
  • 37. Walz‐Cicconi MA, Rose RM, Dammin GJ, Weller TH (1986) Inoculation of guinea pigs with varicella‐zoster virus via the respiratory route. Arch Virol 88: 265–277. [DOI] [PubMed] [Google Scholar]
  • 38. Weller TH, Witton HM, Bell EJ (1958) The etiological agents of varicella and herpes zoster. Isolation, propagation, and culture characteristics in vitro. J Exp Med 108: 843–868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Wenner HA, Abel D, Barrick S, Seshumurty P (1977) Clinical and pathogenetic studies of Medical Lake macaque virus infections in cynomolgus monkeys (simian varicella). J Infect Dis 135: 611–622. [DOI] [PubMed] [Google Scholar]
  • 40. White TM, Mahalingam R, Kolhatkar G, Gilden DH (1997) Identification of simian varicella virus homologues of varicella‐zoster virus genes. Virus Genes 15: 265–269. [DOI] [PubMed] [Google Scholar]
  • 41. Wolf RH, Smetana HF, Allen WP, Felsenfeld AD (1974) Pathology and clinical history of Delta herpesvirus infection in patas monkeys. Lab Anim Sci 24: 218–221. [PubMed] [Google Scholar]
  • 42. Wroblewska Z, Devlin M, Reilly K, van Trieste H, Wellish M, Gilden DH (1982) The production of varicella‐zoster virus antiserum in laboratory animals. Brief report. Arch Virol 74: 233–238. [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES