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Journal of Virology, April 1999, p. 3418-3423, Vol. 73, No. 4
Beckman Research
Institute1 and Department of
Neurology,2 City of Hope National Medical
Center, Duarte, California 91010-3012
Received 23 September 1998/Accepted 8 December 1998
Observation of chronic inflammatory cells and associated high-level
gamma interferon (IFN-
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Role for Gamma Interferon in Control of Herpes
Simplex Virus Type 1 Reactivation
and
) production in ganglia during herpes simplex
type 1 (HSV-1) latent infection in mice (E. M. Cantin, D. R. Hinton, J. Chen, and H. Openshaw, J. Virol. 69:4898-4905, 1995) prompted studies to determine a role of IFN-
in maintaining latency. Mice lacking IFN-
(GKO mice) or the IFN-
receptor (RGKO mice) were inoculated with HSV-1, and the course of the infection was
compared with that in IFN-
-competent mice with the same genetic background (129/Sv//Ev mice). A time course study showed no significant difference in trigeminal ganglionic viral titers or the timing of
establishment of latency. Spontaneous reactivation resulting in
infectious virus in the ganglion did not occur during latency in any of
the mice. However, 24 h after the application of hyperthermic stress to mice, HSV-1 antigens were detected in multiple neurons in the
null mutant mice but in only a single neuron in the 129/Sv//Ev control
mice. Mononuclear inflammatory cells clustered tightly around these
reactivating neurons, and by 48 h, immunostaining was present in
satellite cells as well. The incidence of hyperthermia-induced reactivation as determined by recovery of infectious virus from ganglia
was significantly higher in the null mutant than in control mice: 11%
in 129/Sv//Ev controls, 50% in GKO mice (P = 0.0002), and 33% in RGKO mice (P = 0.03). We concluded that
IFN-
is not involved in the induction of reactivation but rather
contributes to rapid suppression of HSV once it is reactivated.
*
Corresponding author. Mailing address: City of Hope
National Medical Center, Department of Neurology, 1500 E. Duarte Rd., Duarte, CA 91010. Phone: (626) 301-8480. Fax: (626) 301-8852. E-mail:
ecantin{at}.coh.org.
Present address: Harbor UCLA REI Division of Medical Genetics,
Torrance, CA 90502.
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