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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,dagger 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-gamma ) knockout (GKO), and IFN-gamma 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-gamma , 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.

dagger 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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Copyright © 2001 by the American Society for Microbiology. All rights reserved.