We hypothesized that enhanced CD80 expression would result in more eye disease in D22 (
ICP22 null)–infected mice despite the fact that we observed reduced virus replication in mice infected with
ICP22 null virus. We have reported previously that the suppression of CD80 by
ICP22 is dependent on the presence of active virus replication.
22 Therefore, the lack of significant differences between the levels of CD80 expression in TG of latently infected KOS and
ICP22 null viruses is not unexpected. Even though mice infected with
ICP22 null virus display low viral replication, reduced latency, and reduced reactivation, they develop eye disease similar to that seen in KOS-infected mice. The similar influx of immune cell infiltrates into the cornea of
ICP22 null–infected mice in spite of lower viral load is probably the reason why
ICP22 null and KOS display similar levels of eye disease. Therefore, we speculate that despite reduced virus replication, the robust immune response generated by
ICP22 null infection caused equal damage to the corneas of infected mice as did infection with WT virus, even though WT virus has higher virus infectivity. Previous studies
23,24 have shown that in the absence of
ICP22 virus replication is reduced in vitro and in vivo. In contrast to this, previously it has been shown that recombinant HSV-1 with a single mutation in amino acid 34 or 116 of
ICP22 has reduced eye disease, compared with parental control virus.
45,46 This discrepancy between our results and previous studies is possibly due to the fact that, while mutation in amino acid 34 or 116 of
ICP22 affected virus replication and pathology, it did not eliminate its binding to CD80 promoter and thus still did suppress the immune response in the cornea of infected mice. However, in this study, in the absence of
ICP22, there was no suppression of CD80 by
ICP22 and thus we observed more eye disease due to higher immune infiltrates in the cornea of mice infected with
ICP22 null virus than with parental control virus.