Gender influences herpes simplex virus type 1 infection in normal and gamma interferon-mutant mice.
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.
Department of Virology, City of Hope National Medical Center, Duarte, California 91010, USA.
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Han
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Lundberg
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Tanamachi
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Openshaw
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Longmate
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Cantin
D000208:Acute Disease; D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D009154:Mutation; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology; D014775:Virus Activation; D017735:Virus Latency
D013739:Testosterone; D007371:Interferon-gamma