The effect of viral inoculum level and host age on disease incidence, disease severity, and mortality in a murine model of ocular HSV-1 infection

Abstract

It has been previously shown that the strain of virus, immune competence of the host, and innate resistance of the host have an effect on the severity of ocular disease induced by topical infection with herpes simplex virus type 1 (HSV-1). This study has expanded on earlier work by examining the effect of virus inoculum and host age on mortality, incidence of ocular disease, and severity of ocular disease. BALB/c mice were infected with inocula ranging from 2 x 10(3) to 1 x 10(6) pfu of HSV-1 strain CJ394. The most significant effect of variation in the inoculum was on the percent of mice developing disease. Increasing the inoculum resulted in significantly increased disease incidence, but at 5 x 10(3) pfu/mouse or higher, there was little difference in disease severity in those animals exhibiting symptoms. Decreasing host age also resulted in a significant increase in the incidence of ocular disease, but the dependence of disease severity on host age varied with the symptom being scored. In animals exhibiting disease, the peak severity of stromal keratitis and vascularization of the cornea were unaffected by host age. However, the severity of blepharitis was significantly reduced in older mice. Increasing host age also resulted in increased resistance to encephalitis. Three to four-week old mice were very susceptible to encephalitis (100% mortality), while only 20% of 4-5 week old mice died by day 15 post-infection. Mice older than 5 weeks were completely resistant to lethal encephalitis after corneal infection.