Infected peripheral blood mononuclear cells transmit latent varicella zoster virus infection to the guinea pig enteric nervous system

Abstract

Latent wild-type (WT) and vaccine (vOka) varicella zoster virus (VZV) are found in the human enteric nervous system (ENS). VZV also infects guinea pig enteric neurons in vitro, establishes latency and can be reactivated. We therefore determined whether lymphocytes infected in vitro with VZV secrete infectious virions and can transfer infection in vivo to the ENS of recipient guinea pigs. T lymphocytes (CD3-immunoreactive) were preferentially infected following co-culture of guinea pig or human peripheral blood mononuclear cells with VZV-infected HELF. VZV proliferated in the infected T cells and expressed immediate early and late VZV genes. Electron microscopy confirmed that VZV-infected T cells produced encapsulated virions. Extracellular virus, however, was pleomorphic, suggesting degradation occurred prior to release, which was confirmed by the failure of VZV-infected T cells to secrete infectious virions. Intravenous injection of WT- or vOka-infected PBMCs, nevertheless, transmitted VZV to recipient animals (guinea pig > human lymphocytes). Two days post-inoculation, lung and liver, but not gut, contained DNA and transcripts encoding ORFs 4, 40, 66 and 67. Twenty-eight days after infection, gut contained DNA and transcripts encoding ORFs 4 and 66 but neither DNA nor transcripts could any longer be found in lung or liver. In situ hybridization revealed VZV DNA in enteric neurons, which also expressed ORF63p (but not ORF68p) immunoreactivity. Observations suggest that VZV infects T cells, which can transfer VZV to and establish latency in enteric neurons in vivo. Guinea pigs may be useful for studies of VZV pathogenesis in the ENS.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Abreu Velez AM, Smoller BR, Gao W, Grossniklaus HE, Jiao Z, Arias LF, Dudley SC Jr, Howard MS (2012) Varicella-zoster virus (VZV) and alpha 1 antitrypsin: a fatal outcome in a patient affected by endemic pemphigus foliaceus. Int J Dermatol 51:809–816

    Article  PubMed  Google Scholar 

  2. Ali MA, Li Q, Fischer ER, Cohen JI (2009) The insulin degrading enzyme binding domain of varicella-zoster virus (VZV) glycoprotein E is important for cell-to-cell spread and VZV infectivity, while a glycoprotein I binding domain is essential for infection. Virology 386:270–279

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Ambagala AP, Krogmann T, Qin J, Pesnicak L, Cohen JI (2010) A varicella-zoster virus mutant impaired for latency in rodents, but not impaired for replication in cell culture. Virology 399:194–200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Arvin AM, Cohen J (2007) Varicella-zoster virus. In: Fields, (ed) Virology. Raven, pp 2773–2818.

  5. Arvin AM, Moffat JF, Sommer M, Oliver S, Che X, Vleck S, Zerboni L, Ku CC (2010) Varicella-zoster virus T cell tropism and the pathogenesis of skin infection. Curr Top Microbiol Immunol 342:189–209

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Arvin AM, Solem S, Koropchak C, Kinney-Thomas E, Paryani SG (1987) Humoral and cellular immunity to varicella-zoster virus glycoprotein, gpI, and to a non-glycosulated protein p170, in strain 2 guinea pigs. J Gen Virol 68:2449–2454

    Article  CAS  PubMed  Google Scholar 

  7. Asano Y, Itakura N, Kajita Y, Suga S, Yoshikawa T, Yazaki T, Ozaki T, Yamanishi K, Takahashi M (1990) Severity of viremia and clinical findings in children with varicella. J Infect Dis 161:1095–1098

    Article  CAS  PubMed  Google Scholar 

  8. Chang AE, Young NA, Reddick RL, Orenstein JM, Hosea SW, Katz P, Brennan MF (1978) Small bowel obstruction as a complication of disseminated varicella-zoster infection. Surgery 83:371–374

    CAS  PubMed  Google Scholar 

  9. Chen J, Gershon A, Silverstein SJ, Li ZS, Lungu O, Gershon MD (2003) Latent and lytic infection of isolated guinea pig enteric and dorsal root ganglia by varicella zoster virus. J Med Virol 70:S71–S78

    Article  PubMed  Google Scholar 

  10. Chen J, Gershon AA, Li Z, Cowles RA, Gershon MD (2011) Varicella zoster virus (VZV) infects and establishes latency in enteric neurons. J Neurovirol 17:578–589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Chen JJ, Zhu Z, Gershon AA, Gershon MD (2004) Mannose 6-phosphate receptor dependence of varicella zoster virus infection in vitro and in the epidermis during varicella and zoster. Cell 119:915–926

    Article  CAS  PubMed  Google Scholar 

  12. Cohen JI, Krogmann T, Pesnicak L, Ali MA (2007) Absence or overexpression of the Varicella-Zoster Virus (VZV) ORF29 latency-associated protein impairs late gene expression and reduces VZV latency in a rodent model. J Virol 81:1586–1591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Cohrs RJ, Gilden DH (2007) Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia. J Virol 81:2950–2956

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. 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  CAS  PubMed Central  PubMed  Google Scholar 

  15. Debinski HS, Kamm MA, Talbot IC, Khan G, Kangro HO, Jeffries DJ (1997) DNA viruses in the pathogenesis of sporadic chronic idiopathic intestinal pseudo-obstruction. Gut 41:100–106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Edelman DA, Antaki F, Basson MD, Salwen WA, Gruber SA, Losanoff JE (2009) Ogilvie syndrome and herpes zoster: case report and review of the literature. J Emerg Med 39:696–700

    Article  PubMed  Google Scholar 

  17. Folster JM, Jensen NJ, Ruyechan WT, Inoue N, Schmid DS (2011) Regulation of the expression of the varicella-zoster virus open reading frame 66 gene. Virus Res 155:334–342

    Article  CAS  PubMed  Google Scholar 

  18. Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9:286–294

    Article  CAS  PubMed  Google Scholar 

  19. Gabel C, Dubey L, Steinberg S, Gershon M, Gershon A (1989) Varicella-zoster virus glycoproteins are phosphorylated during posttranslational maturation. J Virol 63:4264–4276

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Gan L, Wang M, Yang S, Gershon AA, Chen JJ (2011) Transmission of varicella vaccine virus to a non-family member in China. Vaccine 29:2015–2017

    Article  PubMed  Google Scholar 

  21. Gershon A, Silverstein S (2009) Varicella-zoster virus. In: Richman D, Whitley R, Hayden F (eds) Clinical virology. ASM, Washington DC, pp 451–473

    Google Scholar 

  22. Gershon A, Steinberg S, Silber R (1978) Varicella-zoster viremia. J Pediatr 92:1033–1034

    Article  CAS  PubMed  Google Scholar 

  23. Gershon AA, Chen J, Davis L, Krinsky C, Cowles R, Reichard R, Gershon M (2012) Latency of varicella zoster virus in dorsal root, cranial, and enteric ganglia in vaccinated children. Trans Am Clin Climatol Assoc 123:17–33, discussion 33–5

    PubMed Central  PubMed  Google Scholar 

  24. Gershon AA, Chen J, Gershon MD (2008) A model of lytic, latent, and reactivating varicella-zoster virus infections in isolated enteric neurons. J Infect Dis 197(Suppl 2):S61–S65

    Article  PubMed  Google Scholar 

  25. Gershon AA, Sherman DL, Zhu Z, Gabel CA, Ambron RT, Gershon MD (1994) Intracellular transport of newly synthesized varicella-zoster virus: final envelopment in the trans-Golgi network. J Virol 68:6372–6390

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Gershon M, Gershon A (1999) Role of glycoproteins in varicella-zoster virus infection. In: Wolff MH, Schunemann S, Schmidt A (eds) Varicella-zoster virus, molecular biology, pathogenesis, and clinical aspects. Karger, Basel, pp 43–60

    Google Scholar 

  27. Gershon MD (2005) Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. J Clin Gastroenterol 39:S184–S193

    Article  PubMed  Google Scholar 

  28. Gershon MD (2010) Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci 33:446–456

    Article  CAS  PubMed  Google Scholar 

  29. Gershon MD (2012) Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense. Trans Am Clin Climatol Assoc 123:268–280, discussion 280

    PubMed Central  PubMed  Google Scholar 

  30. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahaliingham R, Cohrs RJ (2000) Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 342:635–645

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Hasnie FS, Breuer J, Parker S, Wallace V, Blackbeard J, Lever I, Kinchington PR, Dickenson AH, Pheby T, Rice AS (2007) Further characterization of a rat model of varicella zoster virus-associated pain: relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs. Neuroscience 144:1495–1508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Hayward A, Burger R, Scheper R, Arvin A (1991) Major histocompatibility complex restriction of T-cell responses to varicella-zoster virus in guinea pigs. J Virol 65:1491–1495

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Hirano I, Pandolfino J (2000) Chronic intestinal pseudo-obstruction. Dig Dis 18:83–92

    Article  CAS  PubMed  Google Scholar 

  35. Holland-Cunz S, Goppl M, Rauch U, Bar C, Klotz M, Schafer KH (2006) Acquired intestinal aganglionosis after a lytic infection with varicella-zoster virus. J Pediatr Surg 41:e29–e31

    Article  PubMed  Google Scholar 

  36. Hood C, Cunningham AL, Slobedman B, Arvin AM, Sommer MH, Kinchington PR, Abendroth A (2006) Varicella-zoster virus ORF63 inhibits apoptosis of primary human neurons. J Virol 80:1025–1031

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Hood C, Cunningham AL, Slobedman B, Boadle RA, Abendroth A (2003) Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: evidence for a cell-type-specific apoptotic response. J Virol 77:12852–12864

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Kennedy PG, Cohrs RJ (2011) Varicella-zoster virus human ganglionic latency: a current summary. J Neurovirol 16:411–418

    Article  Google Scholar 

  39. Kennedy PG, Grinfeld E, Bontems S, Sadzot-Delvaux C (2001) Varicella-Zoster virus gene expression in latently infected rat dorsal root ganglia. Virology 289:218–223

    Article  CAS  PubMed  Google Scholar 

  40. Lake JI, Heuckeroth RO (2013) Enteric nervous system development: migration, differentiation, and disease. Am J Physiol Gastrointest Liver Physiol 305:G1–G24

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Langer JC (2013) Hirschsprung disease. Curr Opin Pediatr 25:368–374

    Article  PubMed  Google Scholar 

  42. Li Q, Ali MA, Cohen JI (2006) Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell 127:305–316

    Article  CAS  PubMed  Google Scholar 

  43. Li Q, Ali MA, Wang K, Sayre D, Hamel FG, Fischer ER, Bennett RG, Cohen JI (2010) Insulin degrading enzyme induces a conformational change in varicella-zoster virus gE, and enhances virus infectivity and stability. PLoS One 5:e11327

    Article  PubMed Central  PubMed  Google Scholar 

  44. Lowry PW, Sabella C, Koropchek C, Watson BN, Thackray HM, Abruzzi GM, Arvin AM (1993) Investigation of the pathogenesis of varicella-zoster virus infection in guinea pigs by using polymerase chain reaction. J Infect Dis 167:78–83

    Article  CAS  PubMed  Google Scholar 

  45. Lowry PW, Solem S, Watson BN, Koropchak C, Thackeray H, Kinchington P, Ruyechan W, Ling P, Hay J, Arvin A (1992) Immunity in strain 2 guinea pigs inoculated with vaccinia virus recombinants expressing varicella-zoster virus glycoproteins I, IV, V, or the protein product of the immediate early gene 62. J Gen Virol 73:811–819

    Article  CAS  PubMed  Google Scholar 

  46. Lungu O, Annunziato P, Gershon A, Stegatis S, Josefson D, LaRussa P, Silverstein S (1995) Reactivated and latent varicella-zoster virus in human dorsal root ganglia. Proc Natl Acad Sci U S A 92:10980–10984

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Lungu O, Panagiotidis C, Annunziato P, Gershon A, Silverstein S (1998) Aberrant intracellular localization of varicella-zoster virus regulatory proteins during latency. Proc Natl Acad Sci U S A 95:7080–7085

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Mahalingham 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 Soc Natl Acad Sci 88:2750–2752

    Article  Google Scholar 

  49. Mahalingham 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 93:2122–2124

    Article  Google Scholar 

  50. Matsunga Y, Yamanishi K, Takahashi M (1982) Experimental infection and immune responses of guinea pigs with varicella zoster virus. Infect Immun 37:407

    Google Scholar 

  51. Moanna A, Rimland D (2013) Decreasing incidence of herpes zoster in the highly active antiretroviral therapy era. Clin Infect Dis 57:122–125

    Article  CAS  PubMed  Google Scholar 

  52. 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

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Myers M, Duer HL, Haulser CK (1980) Experimental infection of guinea pigs with varicella-zoster virus. J Infect Dis 142:414–420

    Article  CAS  PubMed  Google Scholar 

  54. Myers M, Stanberry L (1991) Drug testing for activity against varicella-zoster virus in hairless guinea pigs. Antiviral Res 15:341–344

    Article  CAS  PubMed  Google Scholar 

  55. Myers M, Stanberry L, Edmond B (1985) Varicella-zoster virus infection of strain 2 guinea pigs. J Infect Dis 151:106–113

    Article  CAS  PubMed  Google Scholar 

  56. Myers MG, Connelly B, Stanberry LR (1991) Varicella in hairless guinea pigs. J Infect Dis 163:746–751

    Article  CAS  PubMed  Google Scholar 

  57. Nagel MA, Choe A, Traktinskiy I, Cordery-Cotter R, Gilden D, Cohrs RJ (2011) Varicella-zoster virus transcriptome in latently infected human ganglia. J Virol 85:2276–2287

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Oaklander AL (2008) Mechanisms of pain and itch caused by herpes zoster (shingles). J Pain 9:S10–S18

    Article  PubMed  Google Scholar 

  59. Ouwendijk WJ, Choe A, Nagel MA, Gilden D, Osterhaus AD, Cohrs RJ, Verjans GM (2012) Restricted VZV transcription in human trigeminal ganglia obtained early after death. J Virol 205(7):1178

    Google Scholar 

  60. Ozaki T, Ichikawa T, Matsui Y, Kondo T, Nagai T, Asano Y, Yamanishi K, Takahashi M (1986) Lymphocyte-associated viremia in varicella. J Med Virol 19:249–253

    Article  CAS  PubMed  Google Scholar 

  61. Pui JC, Furth EE, Minda J, Montone KT (2001) Demonstration of varicella-zoster virus infection in the muscularis propria and myenteric plexi of the colon in an HIV-positive patient with herpes zoster and small bowel pseudo-obstruction (Ogilvie's syndrome). Am J Gastroenterol 96:1627–1630

    Article  CAS  PubMed  Google Scholar 

  62. Sabella C, Lowry P, Abbruzzi G, Koropchek C, Kinchington P, Sagedh-Zadeh M, Hay J, Ruyechan W, Arvin A (1993) Immunization with immediate-early tegument protein (open reading frame 62) of varicella-zoster virus protects guinea pigs against virus challenge. J Virol 67:7673–7676

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Sato H, Pesnicak L, Cohen JI (2003a) Use of a rodent model to show that varicella-zoster virus ORF61 is dispensable for establishment of latency. J Med Virol 70(Suppl 1):S79–S81

    Article  CAS  PubMed  Google Scholar 

  64. Sato H, Pesnicak L, Cohen JI (2003b) Varicella-zoster virus ORF47 protein kinase, which is required for replication in human T cells, and ORF66 protein kinase, which is expressed during latency, are dispensable for establishment of latency. J Virol 77:11180–11185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Schaap A, Fortin JF, Sommer M, Zerboni L, Stamatis S, Ku CC, Nolan GP, Arvin AM (2005) T-cell tropism and the role of ORF66 protein in pathogenesis of varicella-zoster virus infection. J Virol 79:12921–12933

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Schaap-Nutt A, Sommer M, Che X, Zerboni L, Arvin AM (2006) ORF66 protein kinase function is required for T-cell tropism of varicella-zoster virus in vivo. J Virol 80:11806–11816

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Sherman RA, Silva J Jr, Gandour-Edwards R (1991) Fatal varicella in an adult: case report and review of the gastrointestinal complications of chickenpox. Rev Infect Dis 13:424–427

    Article  CAS  PubMed  Google Scholar 

  68. Soong W, Schultz JC, Patera AC, Sommer MH, Cohen JI (2000) Infection of human T lymphocytes with varicella-zoster virus: an analysis with viral mutants and clinical isolates. J Virol 74:1864–1870

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Stallings CL, Duigou GJ, Gershon AA, Gershon MD, Silverstein SJ (2006) The cellular localization pattern of Varicella-Zoster virus ORF29p is influenced by proteasome-mediated degradation. J Virol 80:1497–1512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Steain M, Sutherland JP, Rodriguez M, Cunningham AL, Slobedman B, Abendroth A (2014) Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia. J Virol 88:2704–2716

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  72. Tanida E, Izumi M, Abe T, Tsuchiya I, Okuma K, Uchida E, Hidaka A, Hayashi E, Noguchi M, Masui Y, Yoshizawa K, Shirahama K, Kanezaki A (2013) Disseminated varicella-zoster virus infection complicated with severe abdominal pain and colonic pseudo-obstruction. Nihon Shokakibyo Gakkai Zasshi 110:839–845

    PubMed  Google Scholar 

  73. Toudic JP, Piquet MA, Arsene D, Dao T, Verwaerde C (1995) Occlusive syndrome revealing Varicella-zoster virus infection of the digestive system. Gastroenterol Clin Biol 19:453–454

    CAS  PubMed  Google Scholar 

  74. Wang Z-H, Gershon MD, Lungu O, Zhu Z, Mallory S, Arvin A, Gershon A (2001) Essential role played by the C-terminal domain of glycoprotein I in envelopment of varicella-zoster virus in the trans-Golgi network: interactions of glycoproteins with tegument. J Virol 75:323–340

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Watson CP, Deck JH, Morshead C, Van der Kooy D, Evans RJ (1991) Post-herpetic neuralgia: further post-mortem studies of cases with and without pain. Pain 44:105–117

    Article  CAS  PubMed  Google Scholar 

  76. Weller TH (1953) Serial propagation in vitro of agents producing inclusion bodies derived from varicella and herpes zoster. Proc Soc Exp Biol Med 83:340–346

    Article  CAS  PubMed  Google Scholar 

  77. Wroblewska Z, Valyi-Nagy T, Otte J, Dillner A, Jackson A, Sole DP, Fraser NW (1993) A mouse model for varicella-zoster virus latency. Microb Pathog 15:141–151

    Article  CAS  PubMed  Google Scholar 

  78. Wyburn-Mason R (1957) Visceral lesions in herpes zoster. Br Med J 1:678–681

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Xia D, Srinivas S, Sato H, Pesnicak L, Straus SE, Cohen JI (2003) Varicella-zoster virus open reading frame 21, which is expressed during latency, is essential for virus replication but dispensable for establishment of latency. J Virol 77:1211–1218

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Zerboni L, Reichelt M, Arvin A (2010) Varicella-zoster virus neurotropism in SCID mouse-human dorsal root ganglia xenografts. Curr Top Microbiol Immunol.

  81. 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 U S A 104:14086–14091

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Zerboni L, Sobel RA, Lai M, Triglia R, Steain M, Abendroth A, Arvin A (2012) Apparent expression of varicella-zoster virus proteins in latency resulting from reactivity of murine and rabbit antibodies with human blood group a determinants in sensory neurons. J Virol 86:578–583

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Zerboni L, Sobel RA, Ramachandran V, Rajamani J, Ruyechan W, Abendroth A, Arvin A (2010b) Expression of varicella-zoster virus immediate-early regulatory protein IE63 in neurons of latently infected human sensory ganglia. J Virol 84:3421–3430

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Zhu Z, Gershon MD, Ambron R, Gabel C, Gershon AA (1995a) Infection of cells by varicella zoster virus: inhibition of viral entry by mannose 6-phosphate and heparin. Proc Natl Acad Sci U S A 92:3546–3550

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Zhu Z, Gershon MD, Gabel C, Sherman D, Ambron R, Gershon AA (1995b) Entry and egress of VZV: role of mannose 6-phosphate, heparan sulfate proteoglycan, and signal sequences in targeting virions and viral glycoproteins. Neurology 45:S15–S17

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants No. 30872253 from the National Science Foundation of China and R01-DK09394 from the United States Public Health Service National Institutes of Health.

Conflicts of interest

The authors declare that they have no conflict of interest: Lin Gan, Mingli Wang, Jason J. Chen, Michael D. Gershon, and Anne A. Gershon

Author information

Affiliations

Authors

Corresponding author

Correspondence to Michael D. Gershon.

Additional information

Lin Gan and Jason J. Chen contributed equally to the work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gan, L., Wang, M., Chen, J.J. et al. Infected peripheral blood mononuclear cells transmit latent varicella zoster virus infection to the guinea pig enteric nervous system. J. Neurovirol. 20, 442–456 (2014). https://doi.org/10.1007/s13365-014-0259-1

Download citation

Keywords

  • Neurons
  • VZV
  • Dorsal root ganglia
  • Gut
  • T cells
  • Viremia