The process by which herpes simplex virus type 1 (HSV-1) reactivates from latency to cause recurrent herpetic disease is poorly defined. Although considerable circumstantial evidence suggests that ICPO (an HSV-1 transactivator) plays a central role in reactivation, direct evidence to support this hypothesis is lacking. A limiting factor in the study of ICPO mutants in vivo (as with many other HSV-1 mutants) has been that ICPO mutants do not replicate as efficiently as wild-type HSV-1 in animals. Consequently, it is unclear from previous analyses if the decreased reactivation of ICPO- mutant viruses from trigeminal ganglion is due to inefficient neuronal colonization and latent infection, or a requirement for ICPO in HSV-1 reactivation. The goals of the studies proposed herein is to a) develop methods that allow the equal establishment of latency with mutant and wild-type HSV-1 in mice, and using these methods b) obtain definitive evidence to either support or reject the hypothesis that ICPO plays a role in HSV-1 reactivation.
| Halford, W P; Schaffer, P A (2001) ICP0 is required for efficient reactivation of herpes simplex virus type 1 from neuronal latency. J Virol 75:3240-9 |
| Halford, W P; Kemp, C D; Isler, J A et al. (2001) ICP0, ICP4, or VP16 expressed from adenovirus vectors induces reactivation of latent herpes simplex virus type 1 in primary cultures of latently infected trigeminal ganglion cells. J Virol 75:6143-53 |
| Halford, W P; Schaffer, P A (2000) Optimized viral dose and transient immunosuppression enable herpes simplex virus ICP0-null mutants To establish wild-type levels of latency in vivo. J Virol 74:5957-67 |
