Abstract
Purpose :
Previously we have shown that HSV-1 uses CD80 suppression by ICP22 as a mechanism of immune escape to protect the host from increased pathology. In the current study, we investigated what role if any the absence of CD80 has on HSV-1 pathogenicity in vivo and if rescuing the absence of CD80 by using a recombinant HSV-1 expressing murine CD80 will alter this pathogenicity.
Methods :
C57BL/6 and C57BL/6-CD80-/- mice were ocularly infected with 2x105 pfu/eye of HSV-1 strain McKrae, recombinant virus expressing CD80 (HSV-CD80), and its parental virus (dLAT2903) derived for McKrae without corneal scarification. Virus replication in the infected mice eyes (days 1-7), expression of various infiltrates into the corneas on days 3, 5 and 7 and trigeminal ganglia on day 28 post infection (PI) were determined by RT-PCR. In addition, corneal scarring and latency-reactivation were determined in infected mice on day 28 PI.
Results :
Virus replication into the eyes of McKrae infected CD80-/- mice was lower as compared to its WT control counterpart. Virus reactivation was significantly delayed in CD80-/- mice compared with WT control mice, while level of latency was the same between WT and CD80-/- mice. Eye disease was lower in the absence of CD80 in infected mice. Finally, the phenotype of CD80-/- mice was rescued after infection of mice with HSV-CD80 recombinant virus with regards to virus replication into the eye and reactivation.
Conclusions :
Our results suggest that presence of CD80 has a negative effect on virus replication into the eye, eye disease and reactivation. Therefore, suppression of CD80 can have a therapeutic effect on reducing virus replication and reactivation and this may have a positive effect on the host. Consequently, blocking the interaction of HSV-1 with CD80 could be used to temper the immune response and thus reduce HSV-1 induced HSK.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.