Volume 75, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Primary cultures of embryonic murine neurons and newborn mouse astrocytes were inoculated with West Nile virus (WNV) strain NY385-99 to compare the pathogenesis of WNV infection in these types of CNS cells. Two different outcomes were observed. WNV infection in the neurons was rapidly progressive and destructive; within 5 days, all of the neurons were destroyed through apoptosis. WNV infection in the astrocytes evolved more slowly and did not seem to be highly lethal to the cells. The infected astrocytes continued to produce infectious virus (10–10 PFU/mL) for 114 days, in a permissive, persistent infection. During this period, WNV antigen could be shown in the cytoplasm of the infected astrocytes by immunocytochemical assay, transmission electron microscopy of ultrathin sections, and in the cell culture medium by complement fixation test. Our results with this experimental murine cell model indicate that astrocytes can develop chronic or persistent infection with WNV, suggesting that these cells may play a role in the maintenance of WNV in the CNS.


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  1. Ceccaldi PE, Lucas M, Despres P, 2004. New insights on the neuropathogenicity of West Nile virus. FEMS Lett 233 : 1–6. [Google Scholar]
  2. Couderc T, Guivel-Benhassine F, Calaora V, Gosselin AS, Blondel B, 2002. An ex vivo murine model to study poliovirus-induced apoptosis in nerve cells. J Gen Virol 83 : 1925–1930. [Google Scholar]
  3. Heneka MT, Feinstein DL, 2001. Expression and function of inducible nitric oxide synthase in neurons. J Neuroimmunol 114 : 8–18. [Google Scholar]
  4. Kennedy PG, Gairns J, MacLean AR, 2000. Replication of the herpes simplex virus type 1 RL1 mutant 1716 in primary neuronal cell cultures—possible relevance to use as a viral vector. J Neurol Sci 179 : 108–114. [Google Scholar]
  5. Kosugi I, Shinmura Y, Li RY, Aiba-Masago S, Baba S, Miura K, Tsutsui Y, 1998. Murine cytomegalovirus induces apoptosis in noninfected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture. Acta Neuropathol (Berl) 96 : 239–247. [Google Scholar]
  6. Liao CL, Lin YL, Wang JJ, Huang YL, Yeh CT, Ma SH, Chen LK, 1997. Effect of enforced expression of human Bcl-2 on Japanese encephalitis virus-induced apoptosis in cultured cells. J Virol 71 : 5963–5971. [Google Scholar]
  7. Tucker PC, Griffin DE, Choi S, Bui N, Wesselingh S, 1996. Inhibition of nitric oxide synthesis increases mortality in Sindbis virus encephalitis. J Virol 70 : 3972–3977. [Google Scholar]
  8. Jordan I, Briese T, Fischer N, Lau JY, Lipkin WI, 2000. Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells. J Infect Dis 182 : 1214–1217. [Google Scholar]
  9. Liu Y, King N, Kesson A, Blanden RV, Mullbacher A, 1988. West Nile virus infection modulates the expression of class I and class II MHC antigens on astrocytes in vitro. Ann N Y Acad Sci 540 : 483–485. [Google Scholar]
  10. Parquet MC, Kumatori A, Hasebe F, Morita K, Igarashi A, 2001. West Nile virus-induced bax-dependent apoptosis. FEBS Lett 500 : 17–24. [Google Scholar]
  11. Shrestha B, Gottlieb D, Diamond MS, 2003. Infection and injury of neurons by West Nile encephalitis virus. J Virol 77 : 13203–13213. [Google Scholar]
  12. Xiao S-Y, Guzman H, Zhang H, Travassos da Rosa AP, Tesh RB, 2001. West Nile virus infection in the golden hamster (Mesocricetus auratus): A model for West Nile encephalitis. Emerg Infect Dis 7 : 714–721. [Google Scholar]
  13. Diamond MS, Shrestha B, Marri A, Mahan D, Engle M, 2003. B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus. J Virol 77 : 2578–2586. [Google Scholar]
  14. Sampson BA, Ambrosi C, Charlot A, Reiber K, Veress JF, Armbrustmacher V, 2000. The pathology of human West Nile virus infection. Hum Pathol 31 : 527–531. [Google Scholar]
  15. Shieh WJ, Guarner J, Layton M, Fine A, Miller J, Nash D, Campbell GL, Roehrig JT, Gubler DJ, Zaki SR, 2000. The role of pathology in an investigation of an outbreak of West Nile encephalitis in New York, 1999. Emerg Infect Dis 6 : 370–372. [Google Scholar]
  16. Penn RG, Guarner J, Sejvar JJ, Hartman H, McComb RD, Nevins DL, Bhatmazon J, Zaki SR, 2006. Persist neuroinvasive West Nile Virus infection in immunocompromised patient. Clin Infect Dis 42 : 680–683. [Google Scholar]
  17. Pogodina VV, Frolova MP, Malenko GV, Fokina GI, Koreshkova GV, Kiseleva LL, Bochkova NG, Ralph NM, 1983. Study on West Nile virus persistence in monkeys. Arch Virol 75 : 71–86. [Google Scholar]
  18. Roehrig JT, Nash D, Maldin B, Labowitz A, Martin DA, Lanciotti RS, Campbell GL, 2003. Persistence of virus-reactive serum immunoglobulin M antibody in confirmed West Nile virus encephalitis cases. Emerg Infect Dis 9 : 376–379. [Google Scholar]
  19. Brewer GJ, 1997. Isolation and culture of adult rat hippocampal neurons. J Neurosci Methods 71 : 143–155. [Google Scholar]
  20. Moura Neto V, Mallat M, Jeanfet C, 1983. Microheterogeneity of tubulin proteins in neuronal and glial cells from the mouse brain in culture. EMBO J 2 : 1243–1301. [Google Scholar]
  21. McCarthy KD, de Vellis J, 1980. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol 85 : 890–902. [Google Scholar]
  22. Tonry JH, Xiao SY, Siirin M, Chen H, Travassos da Rosa APA, Tesh RE, 2005. Persistent shedding of West Nile vírus in urine of experimentally infected hamsters. Am J Trop Med Hyg 72 : 320–324. [Google Scholar]
  23. Beaty B, Calisher CH, Shope RE, 1995.Arboviruses. Lennette DA, ed. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. Washington, DC: American Public Health Association, 797–855.
  24. Moncayo AC, Hice CL, Watts DM, Travassos da Rosa APA, Guzman H, Russell KL, Calampa C, Gozalo A, Popov VL, Weaver SC, Tesh RB, 2001. Allpahuayo virus: A newly recognized arenavirus (Arenaviridae) from arboreal rice rats (Oecomys bicolor and Oecomys paricola) in Northearstern Peru. Virology 284 : 277–286. [Google Scholar]
  25. Solomon T, Ooi MH, Beasley DWC, Mallewa M, 2003. West Nile encephalitis. BMJ 326 : 865–869. [Google Scholar]
  26. Granwehr BP, Lillibridge KM, Higgs S, Mason PW, Aronson JF, Campbell GA, Barrett ADT, 2004. West Nile virus: Where are we now? Lancet Infect Dis 4 : 547–556. [Google Scholar]

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  • Received : 25 Jan 2006
  • Accepted : 01 Jun 2006

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