We have previously shown that the Igh-1 locus on chromosome 12 of the mouse influences contralateral disease patterns in the modified von-Szily model. Following intracameral injection with 1.5 X 10(4) PFU of HSV strain KOS (HSV-KOS), 75% of BALB/cByJ (Igh-1a), 30% of C.AL-20 (Igh-1d) and 5% of C.B-17 (Igh-1b) mice develop contralateral chorioretinal necrosis. In contrast, Igh-1 congenic mice do not develop contralateral chorioretinal necrosis following anterior chamber inoculation of the same dose of an HSV-KOS mutant lacking surface glycoprotein-C (HSV-GC-KOS). Similarly, injection of wild type HSV strain mP (HSV-mP) into the anterior chamber of susceptible BALB/cByJ mice induces destructive contralateral chorioretinitis whereas injection of the same dose of the mutant HSV strain MP (HSV-MP) lacking surface glycoprotein-C does not induce a destructive contralateral chorioretinitis. In addition, higher doses of HSV-mP inoculum abrogate the Igh-1-associated contralateral chorioretinal protection seen in C.B-17 mice; protection is restored in C.B-17 mice at lower HSV-mP doses that still cause contralateral chorioretinitis in BALB/cByJ mice. These data demonstrate the influence of the viral isolate on the modified von-Szily model and specifically the requirement for the presence of glycoprotein-C on the surface of HSV for the development of contralateral destructive chorioretinitis.