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Journal of Virology, March 2001, p. 3048-3052, Vol. 75, No. 6
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.6.3048-3052.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Gender Influences Herpes Simplex Virus Type 1 Infection in Normal and Gamma Interferon-Mutant Mice
Xiao
Han,1
Patric
Lundberg,1
Becky
Tanamachi,1,
Harry
Openshaw,1,2
Jeff
Longmate,3 and
Edouard
Cantin1,2,*
Departments of
Virology1 and
Neurology2 and Department of
Biostatistics,3 City of Hope National
Medical Center, Duarte, California 91010
Received 19 August 2000/Accepted 20 December 2000
Gender influences the incidence and severity of some bacterial and
viral infections and autoimmune diseases in animal models and humans.
To determine a gender-based difference, comparisons were made between
male and female mice inoculated with herpes simplex virus type 1 (HSV-1) by the corneal route. Mortality was higher in the male mice of
the three strains tested: 129/Sv//Ev wild type, gamma interferon
(IFN-
) knockout (GKO), and IFN-
receptor knockout (RGKO).
Similarly, in vivo HSV-1 reactivation occurred more commonly in male
mice, but the male-female difference in reactivation was restricted to
the two knockout strains and was not seen in the 129/Sv//Ev control.
Comparison among male mice of the three strains showed a higher
mortality of the RGKO mice and a higher reactivation rate of the GKO
and RGKO mice than of the 129/Sv//Ev males. In contrast, female RGKO
and GKO mice did not differ from female 129/Sv//Ev controls in either
mortality or reactivation. HSV-1 periocular and eyelid disease was also more severe in male and dihydrotestosterone (DHT)-treated female mice
than in control female mice. These results show a consistent gender
difference in HSV-1 infection, with a worse outcome in male mice. In
addition, the results comparing GKO and RGKO mice to controls show
differences only in male mice, suggesting that some effects of IFN-
,
a key immunoregulatory molecule, are gender specific.
*
Corresponding author. Mailing address: City of Hope
Medical Center and Beckman Research Institute, Department of Virology, 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.
Journal of Virology, March 2001, p. 3048-3052, Vol. 75, No. 6
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.6.3048-3052.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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