We used CD28−/−, CD28−/− CTLA4−/−, and PD-L1−/− mice to determine possible roles of the CD28-CTLA4-PD-L1 axis and their lack of interaction with CD80 in primary ocular infection, eye disease, and latency reactivation following infection with wild-type HSV-1. The gene discussed is CD28; the disease is infection.