Skip to main content
SpringerLink
Log in

Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts

  • Chapter
  • First Online:
Varicella-zoster Virus

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 342))

Abstract

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arvin AM (2001) Varicella vaccine: genesis, efficacy, and attenuation. Virology 284:153–158

    Article  PubMed  CAS  Google Scholar 

  • Arvin A (2005) Aging, immunity, and the varicella-zoster virus. N Engl J Med 352:2266–2267

    Article  PubMed  CAS  Google Scholar 

  • Arvin AM (2006) Investigations of the pathogenesis of Varicella zoster virus infection in the SCIDhu mouse model. Herpes 13:75–80

    PubMed  Google Scholar 

  • Baiker A, Fabel K, Cozzio A, Zerboni L, Fabel K, Sommer M, Uchida N, He D, Weissman I, Arvin AM (2004) Varicella-zoster virus infection of human neural cells in vivo. Proc Natl Acad Sci USA 101:10792–10797

    Article  PubMed  CAS  Google Scholar 

  • Barden H (1981) The biology and chemistry of neuromelanin. In: Sohal R (ed) Age pigments. Elsevier/North Holland Biomedical Press, Amsterdam, pp 155–180

    Google Scholar 

  • Boeckh M, Kim HW, Flowers ME, Meyers JD, Bowden RA (2006) Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation–a randomized double-blind placebo-controlled study. Blood 107:1800–1805

    Article  PubMed  CAS  Google Scholar 

  • Cohen J, Straus S, Arvin A (2007) Varicella-zoster virus replication, pathogenesis, and management. In: Knipe D, Howley P (eds) Fields virology, vol 2. Lippincott-Williams & Wilkins, Philadelphia, pp 2774–2818

    Google Scholar 

  • Cohrs RJ, Srock K, Barbour MB, Owens G, Mahalingam R, Devlin ME, Wellish M, Gilden DH (1994) Varicella-zoster virus (VZV) transcription during latency in human ganglia: construction of a cDNA library from latently infected human trigeminal ganglia and detection of a VZV transcript. J Virol 68:7900–7908

    PubMed  CAS  Google Scholar 

  • Cohrs RJ, Barbour M, Gilden DH (1996) Varicella-zoster virus (VZV) transcription during latency in human ganglia: detection of transcripts mapping to genes 21, 29, 62, and 63 in a cDNA library enriched for VZV RNA. J Virol 70:2789–2796

    PubMed  CAS  Google Scholar 

  • Cohrs RJ, Randall J, Smith J, Gilden DH, Dabrowski C, van Der Keyl H, Tal-Singer R (2000) Analysis of individual human trigeminal ganglia for latent herpes simplex virus type 1 and varicella-zoster virus nucleic acids using real-time PCR. J Virol 74:11464–11471

    Article  PubMed  CAS  Google Scholar 

  • Cohrs RJ, Gilden DH, Kinchington PR, Grinfeld E, Kennedy PG (2003) Varicella-zoster virus gene 66 transcription and translation in latently infected human Ganglia. J Virol 77:6660–6665

    Article  PubMed  CAS  Google Scholar 

  • Double KL, Dedov VN, Fedorow H, Kettle E, Halliday GM, Garner B, Brunk UT (2008) The comparative biology of neuromelanin and lipofuscin in the human brain. Cell Mol Life Sci 65:1669–1682

    Article  PubMed  CAS  Google Scholar 

  • Esiri MM, Tomlinson AH (1972) Herpes Zoster. Demonstration of virus in trigeminal nerve and ganglion by immunofluorescence and electron microscopy. J Neurol Sci 15:35–48

    Article  PubMed  CAS  Google Scholar 

  • Gilden DH, Vafai A, Shtram Y, Becker Y, Devlin M, Wellish M (1983) Varicella-zoster virus DNA in human sensory ganglia. Nature 306:478–480

    Article  PubMed  CAS  Google Scholar 

  • Gilden DH, Rozenman Y, Murray R, Devlin M, Vafai A (1987) Detection of varicella-zoster virus nucleic acid in neurons of normal human thoracic ganglia. Ann Neurol 22:377–380

    Article  PubMed  CAS  Google Scholar 

  • Gilden D, Mahalingam R, Deitch S, Cohrs RJ (2006) Varicella-zoster virus neuropathogenesis and latency. Caister Academic, Norwich

    Google Scholar 

  • Grinfeld E, Kennedy PG (2004) Translation of varicella-zoster virus genes during human ganglionic latency. Virus Genes 29:317–319

    Article  PubMed  CAS  Google Scholar 

  • Grose C (1981) Variation on a theme by Fenner: the pathogenesis of chickenpox. Pediatrics 68:735–737

    PubMed  CAS  Google Scholar 

  • Hope-Simpson R (1965) The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Soc Med 58:9–20

    PubMed  CAS  Google Scholar 

  • Hyman RW, Ecker JR, Tenser RB (1983) Varicella-zoster virus RNA in human trigeminal ganglia. Lancet 2:814–816

    Article  PubMed  CAS  Google Scholar 

  • Ito H, Sommer MH, Zerboni L, He H, Boucaud D, Hay J, Ruyechan W, Arvin AM (2003) Promoter sequences of varicella-zoster virus glycoprotein I targeted by cellular transactivating factors Sp1 and USF determine virulence in skin and T cells in SCIDhu mice in vivo. J Virol 77:489–498

    Article  PubMed  CAS  Google Scholar 

  • Jones JO, Arvin AM (2006) Inhibition of the NF-kappaB pathway by varicella-zoster virus in vitro and in human epidermal cells in vivo. J Virol 80:5113–5124

    Article  PubMed  CAS  Google Scholar 

  • Kennedy PG, Grinfeld E, Gow JW (1998) Latent varicella-zoster virus is located predominantly in neurons in human trigeminal ganglia. Proc Natl Acad Sci USA 95:4658–4662

    Article  PubMed  CAS  Google Scholar 

  • Kennedy PG, Grinfeld E, Gow JW (1999) Latent Varicella-zoster virus in human dorsal root ganglia. Virology 258:451–454

    Article  PubMed  CAS  Google Scholar 

  • Ku CC, Padilla JA, Grose C, Butcher EC, Arvin AM (2002) Tropism of varicella-zoster virus for human tonsillar CD4(+) T lymphocytes that express activation, memory, and skin homing markers. J Virol 76:11425–11433

    Article  PubMed  CAS  Google Scholar 

  • Ku CC, Zerboni L, Ito H, Graham BS, Wallace M, Arvin AM (2004) Varicella-zoster virus transfer to skin by T cells and modulation of viral replication by epidermal cell interferon-alpha. J Exp Med 200:917–925

    Article  PubMed  CAS  Google Scholar 

  • LaGuardia JJ, Cohrs RJ, Gilden DH (1999) Prevalence of varicella-zoster virus DNA in dissociated human trigeminal ganglion neurons and nonneuronal cells. J Virol 73:8571–8577

    PubMed  CAS  Google Scholar 

  • Levin MJ, Cai GY, Manchak MD, Pizer LI (2003) Varicella-zoster virus DNA in cells isolated from human trigeminal ganglia. J Virol 77:6979–6987

    Article  PubMed  CAS  Google Scholar 

  • Lungu O, Annunziato PW, Gershon A, Staugaitis SM, Josefson D, LaRussa P, Silverstein SJ (1995) Reactivated and latent varicella-zoster virus in human dorsal root ganglia. Proc Natl Acad Sci USA 92:10980–10984

    Article  PubMed  CAS  Google Scholar 

  • Lungu O, Panagiotidis CA, Annunziato PW, Gershon AA, Silverstein SJ (1998) Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency. Proc Natl Acad Sci USA 95:7080–7085

    Article  PubMed  CAS  Google Scholar 

  • Mahalingam R, Wellish M, Lederer D, Forghani B, Cohrs R, Gilden D (1993) Quantitation of latent varicella-zoster virus DNA in human trigeminal ganglia by polymerase chain reaction. J Virol 67:2381–2384

    PubMed  CAS  Google Scholar 

  • Mahalingam R, Wellish M, Cohrs R, Debrus S, Piette J, Rentier B, Gilden DH (1996) Expression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons. Proc Natl Acad Sci USA 93:2122–2124

    Article  PubMed  CAS  Google Scholar 

  • Mallory S, Sommer M, Arvin AM (1997) Mutational analysis of the role of glycoprotein I in varicella-zoster virus replication and its effects on glycoprotein E conformation and trafficking. J Virol 71:8279–8288

    PubMed  CAS  Google Scholar 

  • Manuel O, Kumar D, Singer LG, Cobos I, Humar A (2008) Incidence and clinical characteristics of herpes zoster after lung transplantation. J Heart Lung Transplant 27:11–16

    Article  PubMed  Google Scholar 

  • McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL (1988) The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 241:1632–1639

    Article  PubMed  CAS  Google Scholar 

  • Meier JL, Holman RP, Croen KD, Smialek JE, Straus SE (1993) Varicella-zoster virus transcription in human trigeminal ganglia. Virology 193:193–200

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Moffat JF, Zerboni L, Kinchington PR, Grose C, Kaneshima H, Arvin AM (1998) Attenuation of the vaccine Oka strain of varicella-zoster virus and role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse. J Virol 72:965–974

    PubMed  CAS  Google Scholar 

  • Moffat J, Ito H, Sommer M, Taylor S, Arvin AM (2002) Glycoprotein I of varicella-zoster virus is required for viral replication in skin and T cells. J Virol 76:8468–8471

    Article  PubMed  CAS  Google Scholar 

  • Mosier DE, Gulizia RJ, Baird SM, Wilson DB (1988) Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–259

    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 varicella-zoster 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 MH, Ito H, Hinchliffe S, Arvin AM (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  Google Scholar 

  • Oliver SL, Zerboni L, Sommer M, Rajamani J, Arvin AM (2008) Development of recombinant varicella-zoster viruses expressing luciferase fusion proteins for live in vivo imaging in human skin and dorsal root ganglia xenografts. J Virol Methods 154:182–193

    Article  PubMed  CAS  Google Scholar 

  • Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2284

    Article  PubMed  CAS  Google Scholar 

  • Pevenstein SR, Williams RK, McChesney D, Mont EK, Smialek JE, Straus SE (1999) Quantitation of latent varicella-zoster virus and herpes simplex virus genomes in human trigeminal ganglia. J Virol 73:10514–10518

    PubMed  CAS  Google Scholar 

  • Quinlivan ML, Gershon AA, Al Bassam MM, Steinberg SP, LaRussa P, Nichols RA, Breuer J (2007) Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts. Proc Natl Acad Sci USA 104:208–212

    Article  PubMed  CAS  Google Scholar 

  • Reichelt M, Zerboni L, Arvin AM (2008) Mechanisms of varicella-zoster virus neuropathogenesis in human dorsal root ganglia. J Virol 82:3971–3983

    Article  PubMed  CAS  Google Scholar 

  • Silverstein S, Straus S (2000) Pathogenesis of latency and reactivation. In: Arvin A, Gershon A (eds) Varicella zoster virus: virology and clinical management. Cambridge University Press, Cambridge, pp 123–141

    Chapter  Google Scholar 

  • Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T (1974) Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 2:1288–1290

    Article  PubMed  CAS  Google Scholar 

  • Tischer BK, Kaufer BB, Sommer M, Wussow F, Arvin AM, Osterrieder N (2007) A self-excisable infectious bacterial artificial chromosome clone of varicella-zoster virus allows analysis of the essential tegument protein encoded by ORF9. J Virol 81:13200–13208

    Article  PubMed  CAS  Google Scholar 

  • Wang K, Lau TY, Morales M, Mont EK, Straus SE (2005) Laser-capture microdissection: refining estimates of the quantity and distribution of latent herpes simplex virus 1 and varicella-zoster virus DNA in human trigeminal ganglia at the single-cell level. J Virol 79:14079–14087

    Article  PubMed  CAS  Google Scholar 

  • Zerboni L, Sommer M, Ware CF, Arvin AM (2000) Varicella-zoster virus infection of a human CD4-positive T-cell line. Virology 270:278–285

    Article  PubMed  CAS  Google Scholar 

  • Zerboni L, Hinchliffe S, Sommer MH, Ito H, Besser J, Stamatis S, Cheng J, Distefano D, Kraiouchkine N, Shaw A, Arvin AM (2005a) Analysis of varicella zoster virus attenuation by evaluation of chimeric parent Oka/vaccine Oka recombinant viruses in skin xenografts in the SCIDhu mouse model. Virology 332:337–346

    Article  PubMed  CAS  Google Scholar 

  • Zerboni L, Ku CC, Jones CD, Zehnder JL, Arvin AM (2005b) Varicella-zoster virus infection of human dorsal root ganglia in vivo. Proc Natl Acad Sci USA 102:6490–6495

    Article  PubMed  CAS  Google Scholar 

  • Zerboni L, Reichelt M, Jones CD, Zehnder JL, Ito H, Arvin AM (2007) From the Cover: Aberrant infection and persistence of varicella-zoster virus in human dorsal root ganglia in vivo in the absence of glycoprotein I. Proc Natl Acad Sci USA 104:14086–14091

    Article  PubMed  CAS  Google Scholar 

  • Zerboni L, Arvin A (2008) The pathogenesis of varicella-zoster virus neurotropism and infection. In: Reiss C (ed) Neurotropic viral infections. Cambridge University Press, Cambridge, pp 225–251

    Chapter  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  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stanford University Medical Center, Stanford, CA, USA

    L. Zerboni, M. Reichelt & A. Arvin

Authors
  1. L. Zerboni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Reichelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Arvin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Zerboni .

Editor information

Editors and Affiliations

  1. Department of Infectious Diseases and Im, Head, VZV Research Laboratory, University of Sydney, Room 601 Blackburn Building D06, Sydney, 2006, New South Wales, Australia

    Allison Abendroth

  2. School of Medicine, Dept. Microbiology & Immunology, Stanford University, Pasteur Drive 300, Stanford, 94305-5124, California, USA

    Ann M. Arvin

  3. 2215 Weiskotten Hall, Upstate Medical University, East Adams Street 750, Syracuse, 13210, New York, USA

    Jennifer F. Moffat

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Zerboni, L., Reichelt, M., Arvin, A. (2010). Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts. In: Abendroth, A., Arvin, A., Moffat, J. (eds) Varicella-zoster Virus. Current Topics in Microbiology and Immunology, vol 342. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2009_8

Download citation

Publish with us

Policies and ethics

Search

Navigation