Our results suggest that (i) the absence of CD80 reduced both virus replication in the eye of CD80−/− mice on day 5 post-infection (PI) and gB expression in their trigeminal ganglia (TG) on day 3 PI; (ii) in the absence of CD80, virus reactivation in TG of latently infected mice was slower than in control mice; (iii) latency and survival were similar in CD80−/− mice and WT mice; and (iv) CD80−/− mice had significantly more CD8 T cells and higher PD-L1 expression than WT mice, which did not correlate with higher levels of PD-1 expression in TG of latently infected mice. Here, CD80 is linked to infection.