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

It has been previously shown that the strain of virus, immune competen ce of the host, and innate resistance of the host have an effect on th e 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, i ncidence of ocular disease, and severity of ocular disease. BALB/c mic e were infected with inocula ranging from 2X10(3) to 1X10(6) pfu of HS V-1 strain CJ394. The most significant effect of variation in the inoc ulum was on the percent of mice developing disease. Increasing the ino culum resulted in significantly increased disease incidence, but at 5X 10(3) pfu/mouse or higher, there was little difference in disease seve rity in those animals exhibiting symptoms. Decreasing host age also re sulted in a significant increase in the incidence of ocular disease, b ut the dependence of disease severity on host age varied with the symp tom 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 redu ced in older mice. Increasing host age also resulted in increased resi stance to encephalitis. Three to four-week old mice were very suscepti ble to encephalitis (100% mortality), while only 20% of 4-5 week old m ice died by day 15 post-infection. Mice older than 5 weeks were comple tely resistant to lethal encephalitis after corneal infection.