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 in fections and autoimmune diseases in animal models and humans. To determine a gender-based difference, comparisons were made between male and female mi ce 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 mo re commonly in male mice, but the male-female difference in reactivation wa s 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 m ortality of the RGKO mite and a higher reactivation rate of the GKO and RGK O 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 react ivation. HSV-1 periocular and eyelid disease was also more severe in male a nd dihydrotestosterone (DHT)-treated female mice than in control female mic e. These results show a consistent gender difference in HSV-1 infection, wi th 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 s ome effects,of IFN-gamma, a key immunoregulatory molecule, are gender speci fic.