Abstract
Purpose :
Our published studies and our analyses of ocular HSV-1 infection and recurrence have generated compelling results indicating that the latency-associated transcript (LAT) of HSV-1 modulates the effects of type I IFN induction. IFNa2A, also called IFNa2 (Roferon-A) is well characterized and broadly expressed and has been used in monotherapy or in combination therapy with other drugs in treating viral infections and different kinds of cancer. The goal of this study was to determine if the absence of IFNa2 affect primary and latent infection in ocularly infected mice
Methods :
We recently generated a mouse strain lacking IFNa2 expression (IFNa2-/-).
Ocular HSV-1 replication, eye disease, survival, and latency-reactivation was evaluated in ocularly infected IFNα2-/- and WT mice. Individual TG from surviving mice were isolated on day 28 post-infection (PI) and used for detection of viral DNA, RNA, for the presence of viral antigens, and exhaustion markers by FACS, RT-PCR, and immunostaining.
Results :
We compared IFNα2-/- mice with WT control mice after HSV-1 infection. IFNa2-/- mice had significantly less HSV-1 gB, IFNγ, GZMB, CD8α and CD11c expression in both corneas and TG on day 5 PI compared to WT mice. The absence of IFNα2 did not affect the levels of the other 13 members of IFNα family. Virus replication into the eyes of ocularly infected IFNα2-/- mice, eye disease and survival were similar to WT infected mice. The absence of IFNα2 reduced the levels of latency and T cell exhaustion but not time to reactivation compared with control mice.
Conclusions :
We have reported for the first time the construction of a knockout mouse lacking IFNa2 (Roferon-A) gene. The absence of IFNa2 affected levels of viral transcripts as well as reduced levels of latency. Our results also suggest that few but not all functions of IFNa2 could be compensated by the remaining 13 members of IFNa family.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.