Journal of Virology, December 2003, p. 13203-13213, Vol. 77, No. 24
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.24.13203-13213.2003
Copyright © 2003, American
Society for
Microbiology. All Rights Reserved.
Infection and Injury of Neurons by West Nile Encephalitis Virus
Bimmi Shrestha,1 David Gottlieb,2 and Michael S. Diamond1,3,4*
Departments
of Medicine,1
Pathology and
Immunology,3
Molecular
Microbiology,4
Anatomy and
Neurobiology, Washington University School of Medicine,
St. Louis, Missouri2
Received 27 June 2003/
Accepted 12 September 2003
West
Nile virus (WNV) infects neurons and leads to encephalitis, paralysis,
and death in humans, animals, and birds. We investigated the mechanism
by which neuronal injury occurs after WNV infection. Neurons in the
anterior horn of the spinal cords of paralyzed mice exhibited a high
degree of WNV infection, leukocyte infiltration, and degeneration.
Because it was difficult to distinguish whether neuronal injury was
caused by viral infection or by the immune system response, a novel
tissue culture model for WNV infection was established in neurons
derived from embryonic stem (ES) cells. Undifferentiated ES cells were
relatively resistant to WNV infection. After differentiation, ES cells
expressed neural antigens, acquired a neuronal phenotype, and became
permissive for WNV infection. Within 48 h of exposure to an
exceedingly low multiplicity of infection (5 x
10-4), 50% of ES cell-derived neurons became
infected, producing nearly 107 PFU of infectious virus per
ml, and began to die by an apoptotic mechanism. The establishment of a
tractable virus infection model in ES cell-derived neurons facilitates
the study of the molecular basis of neurotropism and the mechanisms of
viral and immune-mediated neuronal injury after infection by WNV or
other neurotropic
pathogens.
* Corresponding
author. Mailing address: Departments of Medicine, Molecular
Microbiology, and Pathology and Immunology, Washington University
School of Medicine, 660 South Euclid Ave., Box 8051, St. Louis, MO
63110. Phone: (314) 362-2842. Fax: (314) 362-9230. E-mail:
diamond{at}borcim.wustl.edu.
Journal of Virology, December 2003, p. 13203-13213, Vol. 77, No. 24
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.24.13203-13213.2003
Copyright © 2003, American
Society for
Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.