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Journal of Virology, June 2001, p. 5252-5262, Vol. 75, No. 11
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.11.5252-5262.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Tracking the Spread of a lacZ-Tagged
Herpes Simplex Virus Type 1 between the Eye and the Nervous System of
the Mouse: Comparison of Primary and Recurrent Infection
Carolyn
Shimeld,1,*
Stacey
Efstathiou,2 and
Terry
Hill3
Division of
Ophthalmology1 and Department of
Pathology and Microbiology,3 University of
Bristol, Bristol BS8 1TD, and Division of Virology, University
of Cambridge, Cambridge CB2 1QP,2 United Kingdom
Received 5 December 2000/Accepted 2 March 2001
The spread of herpes simplex virus type 1 (HSV-1) during primary
ocular infection and after reactivation of latent infection in the
trigeminal ganglion (TG) was examined in the mouse using a genetically
modified virus containing the lacZ reporter gene under the
control of the immediate-early 110 promoter. Whole tissue mounts of the
eye and lids, their sensory nerves, and TG with the attached dorsal
root entry zone (DRE) into the central nervous system (CNS) were
stained for
-galactosidase. Sixteen hours after inoculation of the
cornea by scarification, staining was found in the scarified epithelium
of the cornea and in the unscarified conjunctiva. By 24 h,
staining was also seen in a few TG neurons and by 96 h their
number had greatly increased and their distribution was more
widespread. Stained cells (identified as Schwann cells by their
staining for glial fibrillary acidic protein [GFAP] or S-100) in the
TG were first seen close to stained neurons at 40 h, and by
48 h lines of such cells extended partway toward the periphery and
toward the DRE. By 72 h, these lines had reached the periphery and
the DRE where the adjacent CNS was also stained. In the cornea, stained
cells with the morphology and arrangement of Schwann cells were seen
from 40 to 120 h. After reactivation of latent infection, 10 of 22 samples had positively stained neurons. In eight samples, corneal and
lid epithelial cells were stained. No stained Schwann cells were seen
in the TG; however, branched networks of such cells were present in the
cornea and the lids. This detailed sequential analysis has provided new
information on the involvement of Schwann cells in the pathogenesis of
primary and recurrent HSV-1 disease in the TG and the cornea.
*
Corresponding author. Mailing address: Division of
Ophthalmology, School of Medical Sciences, University of Bristol,
University Walk, Bristol BS8 1TD, United Kingdom. Phone:
44-117-9287627. Fax: 44-117-9287896. E-mail:
C.Shimeld{at}bris.ac.uk.
Journal of Virology, June 2001, p. 5252-5262, Vol. 75, No. 11
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.11.5252-5262.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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