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Varicella zoster virus vaccines: potential complications and possible improvements

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Virologica Sinica

Abstract

Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.

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References

  • Abendroth A, Arvin A. 1999. Varicella-zoster virus immune evasion. Immunological reviews, 168: 143–156.

    Article  PubMed  CAS  Google Scholar 

  • Arvin A M. 1995. Aspects of the host response to varicella-zoster virus: a review of recent observations. Neurology, 45: S36–37.

    Article  PubMed  CAS  Google Scholar 

  • Arvin A M. 2001. Varicella-zoster virus: molecular virology and virus-host interactions. Curr Opin Microbiol, 4: 442–449.

    Article  PubMed  CAS  Google Scholar 

  • Chesnut G, McClain D, Galeckas K. 2012. Varicella-zoster virus in children immunized with the varicella vaccine. Cutis, 90: 114–116.

    PubMed  Google Scholar 

  • Choo P W, Donahue J G, Manson J E, Platt R. 1995. The epide-miology of varicella and its complications. J Infect Dis, 172: 706–712.

    Article  PubMed  CAS  Google Scholar 

  • Cohen J I, Seidel K E. 1993. Generation of varicella-zoster virus (VZV) and viral mutants from cosmid DNAs: VZV thymidylate synthetase is not essential for replication in vitro. Proc Natl Acad Sci U S A, 90: 7376–7380.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Cole N L, Grose C. 2003. Membrane fusion mediated by herpesvirus glycoproteins: the paradigm of varicella-zoster virus. Rev Med Virol, 13: 207–222.

    Article  PubMed  CAS  Google Scholar 

  • Collaco A M, Rahman S, Dougherty E J, Williams B B, Geusz M E. 2005. Circadian regulation of a viral gene promoter in live transgenic mice expressing firefly luciferase. Mol Imaging Biol, 7: 342–350.

    Article  PubMed  Google Scholar 

  • Contag C H, Bachmann M H. 2002. Advances in in vivo bioluminescence imaging of gene expression. Annu Rev Biomed Eng, 4: 235–260.

    Article  PubMed  CAS  Google Scholar 

  • Contag C H, Spilman S D, Contag P R, Oshiro M, Eames B, Dennery P, Stevenson D K, Benaron D A. 1997. Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol, 66: 523–531.

    Article  PubMed  CAS  Google Scholar 

  • Doyle T C, Burns S M, Contag C H. 2004. In vivo bioluminescence imaging for integrated studies of infection. Cell Microbiol, 6: 303–317.

    Article  PubMed  CAS  Google Scholar 

  • Drolet M, Brisson M, Schmader K E, Levin M J, Johnson R, Oxman M N, Patrick D, Blanchette C, Mansi J A. 2010. The impact of herpes zoster and postherpetic neuralgia on healthrelated quality of life: a prospective study. CMAJ: Canadian Medical Association journal = journal de l’Association medicale canadienne, 182: 1731–1736.

    Article  Google Scholar 

  • Dulal K, Zhang Z, Zhu H. 2009. Development of a gene capture method to rescue a large deletion mutant of human cytomegalovirus. Journal of Virological Methods, 157: 180–187.

    Article  PubMed  CAS  Google Scholar 

  • Dulal K, Silver B, Zhu H. 2012. Use of Recombination-Mediated Genetic Engineering for Construction of Rescue Human Cytomegalovirus Bacterial Artificial Chromosome Clones. Biomed and Biotechnol.

    Google Scholar 

  • Fan S, Maguire C A, Ramirez S H, Bradel-Tretheway B, Sapinoro R, Sui Z, Chakraborty-Sett S, Dewhurst S. 2005. Valproic acid enhances gene expression from viral gene transfer vectors. J Virol Methods, 125: 23–33.

    Article  PubMed  CAS  Google Scholar 

  • Gershon M D, Gershon A A. 2010. VZV infection of keratinocytes: production of cell-free infectious virions in vivo. Curr Top Microbiol Immunol, 342: 173–188.

    PubMed  CAS  Google Scholar 

  • Gilden D H, Kleinschmidt-DeMasters B K, LaGuardia J J, Mahalingam R, Cohrs R J. 2000. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med, 342: 635–645.

    Article  PubMed  CAS  Google Scholar 

  • Harnisch J P. 1984. Zoster in the elderly: clinical, immunologic and therapeutic considerations. J Am Geriatr Soc, 32: 789–793.

    PubMed  CAS  Google Scholar 

  • Hastings J W. 1983. Biological diversity, chemical mechanisms, and the evolutionary origins of bioluminescent systems. J Mol Evol, 19: 309–321.

    Article  PubMed  CAS  Google Scholar 

  • Hatchette T, Tipples G A, Peters G, Alsuwaidi A, Zhou J, Mailman T L. 2008. Foscarnet salvage therapy for acyclovir-resistant varicella zoster: report of a novel thymidine kinase mutation and review of the literature. Pediatr Infect Dis J, 27: 75–77.

    Article  PubMed  Google Scholar 

  • Kimberlin D W, Whitley R J. 2007. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med, 356: 1338–1343.

    Article  PubMed  CAS  Google Scholar 

  • Klassen T P, Hartling L, Wiebe N, Belseck E M. 2005. Acyclovir for treating varicella in otherwise healthy children and adolescents. Cochrane Database Syst Rev: CD002980.

    Google Scholar 

  • Kurfurst M, Ghisla S, Hastings J W. 1983. Bioluminescence emission from the reaction of luciferase-flavin mononucleotide radical with O2. Biochemistry, 22: 1521–1525.

    Article  PubMed  CAS  Google Scholar 

  • Leung J, Harpaz R, Molinari N A, Jumaan A, Zhou F. 2011. Herpes zoster incidence among insured persons in the United States, 1993–2006: evaluation of impact of varicella vaccination. Clin Infect Dis, 52: 332–340.

    Article  PubMed  Google Scholar 

  • Liesegang T J. 2004. Herpes zoster virus infection. Curr Opin Ophthalmol, 15: 531–536.

    Article  PubMed  Google Scholar 

  • Lydick E, Epstein R S, Himmelberger D, White C J. 1995. Herpes zoster and quality of life: a self-limited disease with severe impact. Neurology, 45: S52–53.

    Article  PubMed  CAS  Google Scholar 

  • Nagaike K, Mori Y, Gomi Y, Yoshii H, Takahashi M, Wagner M, Koszinowski U, Yamanishi K. 2004. Cloning of the varicellazoster virus genome as an infectious bacterial artificial chromosome in Escherichia coli. Vaccine, 22: 4069–4074.

    Article  PubMed  CAS  Google Scholar 

  • Niizuma T, Zerboni L, Sommer M H, Ito H, Hinchliffe S, Arvin A M. 2003. Construction of varicella-zoster virus recombinants from parent Oka cosmids and demonstration that ORF65 protein is dispensable for infection of human skin and T cells in the SCID-hu mouse model. J Virol, 77: 6062–6065.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Opstelten W, Mauritz J W, de Wit N J, van Wijck A J, Stalman W A, van Essen G A. 2002. Herpes zoster and postherpetic neuralgia: incidence and risk indicators using a general practice research database. Fam Pract, 19: 471–475.

    Article  PubMed  Google Scholar 

  • Rehemtulla A, Stegman L D, Cardozo S J, Gupta S, Hall D E, Contag C H, Ross B D. 2000. Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia, 2: 491–495.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Reichelt M, Zerboni L, Arvin A M. 2008. Mechanisms of varicellazoster virus neuropathogenesis in human dorsal root ganglia. J Virol, 82: 3971–3983.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Saksena M M, Wakisaka H, Tijono B, Boadle R A, Rixon F, Takahashi H, Cunningham A L. 2006. Herpes simplex virus type 1 accumulation, envelopment, and exit in growth cones and varicosities in mid-distal regions of axons. J Virol, 80: 3592–3606.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Uebe B, Sauerbrei A, Burdach S, Horneff G. 2002. Herpes zoster by reactivated vaccine varicella zoster virus in a healthy child. Eur J Pediatr, 161: 442–444.

    Article  PubMed  Google Scholar 

  • Vazquez M. 2004. Varicella zoster virus infections in children after the introduction of live attenuated varicella vaccine. Curr Opin Pediatr, 16: 80–84.

    Article  PubMed  Google Scholar 

  • Warden C, Tang Q, Zhu H. 2011. Herpesvirus BACs: past, present, and future. J Biomed Biotechnol, 2011: 124595.

    Article  PubMed  PubMed Central  Google Scholar 

  • Warming S, Costantino N, Court D L, Jenkins N A, Copeland N G. 2005. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res, 33: e36.

    Article  PubMed  PubMed Central  Google Scholar 

  • White M R, Masuko M, Amet L, Elliott G, Braddock M, Kingsman A J, Kingsman S M. 1995. Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells. J Cell Sci, 108( Pt 2): 441–455.

    PubMed  CAS  Google Scholar 

  • Whitley R J. 2005. Changing dynamics of varicella-zoster virus infections in the 21st century: the impact of vaccination. J Infect Dis, 191: 1999–2001.

    Article  PubMed  Google Scholar 

  • Yih W K, Brooks D R, Lett S M, Jumaan A O, Zhang Z, Clements K M, Seward J F. 2005. The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003. BMC Public Health, 5: 68.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zerboni L, Arvin A. 2011. Investigation of varicella-zoster virus neurotropism and neurovirulence using SCID mouse-human DRG xenografts. J Neurovirol, 17: 570–577.

    Article  PubMed  CAS  Google Scholar 

  • Zerboni L, Reichelt M, Arvin A. 2010. Varicella-zoster virus neurotropism in SCID mouse-human dorsal root ganglia xenografts. Curr Top Microbiol Immunol, 342: 255–276.

    PubMed  CAS  Google Scholar 

  • Zhang Y, Muyrers J P, Testa G, Stewart A F. 2000. DNA cloning by homologous recombination in Escherichia coli. Nat Biotechnol, 18: 1314–1317.

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Huang Y, Zhu H. 2008. A highly efficient protocol of generating and analyzing VZV ORF deletion mutants based on a newly developed luciferase VZV BAC system. J Virol Methods, 148: 197–204.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang Z, Rowe J, Wang W, Sommer M, Arvin A, Moffat J, Zhu H. 2007. Genetic analysis of varicella-zoster virus ORF0 to ORF4 by use of a novel luciferase bacterial artificial chromosome system. J Virol, 81: 9024–9033.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang Z, Selariu A, Warden C, Huang G, Huang Y, Zaccheus O, Cheng T, Xia N, Zhu H. 2010. Genome-wide mutagenesis reveals that ORF7 is a novel VZV skin-tropic factor. PLoS pathogens, 6: e1000971.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, Biochemistry & Molecular Genetics, Rutgers - New Jersey Medical School, Newark, New Jersey, 07103, USA

    Benjamin Silver & Hua Zhu

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  1. Benjamin Silver
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  2. Hua Zhu
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Correspondence to Hua Zhu.

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Silver, B., Zhu, H. Varicella zoster virus vaccines: potential complications and possible improvements. Virol. Sin. 29, 265–273 (2014). https://doi.org/10.1007/s12250-014-3516-9

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  • DOI: https://doi.org/10.1007/s12250-014-3516-9

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