The Alphaherpesvirinae subfamily is comprised of many important pathogens of humans and animals, including herpes simplex virus 1 and 2, varicella zoster virus, and Marek's disease virus. Equine herpes virus 1 (EHV) is an important, and interesting, pathogen of equines as the outcomes of infection vary from severe respiratory disease, abortigenic disease often leading to reproductive failure, severe neurological disorders, and/or latency. In the laboratory, EHV offers ideal models to investigate the molecular biology, immunology, and pathogenesis of Alphaherpesviruses. EHV infections in cell culture vary from a cytocidal infection to a state of persistent infection. The latter is mediated by defective interfering particles (DIP) whose genome encodes only three proteins, one being a unique hybrid protein derived from portions of two early regulatory genes, EICP22 and EICP2 7. In cytolytic infection, the EICP22P (protein) significantly enhances transactivation of all classes of EHV promoters by interacting with the IE (immediate early) protein. However, in persistent infection the 22/27 hybrid protein trans-represses several classes of EHV promoters. The precise mechanism(s) by which the EICP22P acts as both a trans-activator and trans-repressor remain unclear. The Applicant's overall goal is to employ models of cytocidal and persistent infection (mediated by EHV enriched for DIP) to define the contrasting functions and roles of the EICP22P in these two different outcomes of infection. Information gained from these studies may be useful in the prevention, diagnosis, and treatment of Alphaherpesvirus infections and will give insight into events leading to the establishment of persistent infection.
| Breitenbach, Jonathan E; Ebner, Paul D; O'Callaghan, Dennis J (2009) The IR4 auxiliary regulatory protein expands the in vitro host range of equine herpesvirus 1 and is essential for pathogenesis in the murine model. Virology 383:188-94 |
| Ebner, Paul D; Kim, Seong K; O'Callaghan, Dennis J (2008) Biological and genotypic properties of defective interfering particles of equine herpesvirus 1 that mediate persistent infection. Virology 381:98-105 |
