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J Virol, May 1998, p. 3711-3719, Vol. 72, No. 5
Center for Neurovirology, Department of
Microbiology and Immunology, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107-6799,1 and
Department of Anatomy and Cell Biology, University of
Marburg, D-35033 Marburg, Germany2
Received 24 October 1997/Accepted 23 January 1998
To investigate the involvement of various cellular and humoral
aspects of immunity in the clearance of rabies virus from the central
nervous system, (CNS), we studied the development of clinical signs and
virus clearance from the CNS in knockout mice lacking either B and T
cells, CD8+ cytotoxic T cells, B cells, alpha/beta
interferon (IFN-
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Collaboration of Antibody and Inflammation in
Clearance of Rabies Virus from the Central Nervous System
/
) receptors, IFN-
receptors, or
complement components C3 and C4. Following intranasal
infection with the attenuated rabies virus CVS-F3, normal adult
mice of different genetic backgrounds developed a transient disease
characterized by loss of body weight and appetite depression which
peaked at 13 days postinfection (p.i.). While these animals
had completely recovered by day 21 p.i., mice lacking either B and
T cells or B cells alone developed a progressive disease and succumbed
to infection. Mice lacking either CD8+ T cells, IFN
receptors, or complement components C3 and C4 showed no significant
differences in the development of clinical signs by comparison with
intact counterparts having the same genetic background. However, while
infectious virus and viral RNA could be detected in normal control mice
only until day 8 p.i., in all of the gene knockout mice studied
except those lacking C3 and C4, virus infection persisted through day
21 p.i. Analysis of rabies virus-specific antibody production
together with histological assessment of brain inflammation in infected
animals revealed that clearance of CVS-F3 by 21 days p.i. correlated
with both a strong inflammatory response in the CNS early in the
infection (day 8 p.i.), and the rapid (day 10 p.i.)
production of significant levels of virus-neutralizing antibody (VNA).
These studies confirm that rabies VNA is an absolute requirement for
clearance of an established rabies virus infection. However, for the
latter to occur in a timely fashion, collaboration between VNA and
inflammatory mechanisms is necessary.
*
Corresponding author. Mailing address: Center for
Neurovirology, Department of Microbiology and Immunology, Thomas
Jefferson University, 1020 Locust St., Philadelphia, PA 19107-6799. Phone: (215) 503-4692. Fax: (215) 923-7145. E-mail:
bdietzschold{at}reddi1.uns.tju.edu.
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