PRV is a member of the alphaherpesvirus subfamily along with varicella-zoster virus (VZV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), monkey B virus and bovine herpesvirus type 1 (BHV-1). There is significant conservation of sequence and function amongst the alphaherpesviruses and the majority of these viruses exhibit a predilection for infection of the peripheral nervous system (PNS) and central nervous system (CNS) of their host species. Studies performed with wild-type PRV strain (PRV-Becker) compared to an avirulent, live vaccine PRV strain (PRV-Bartha) have demonstrated that, of all the known mutations in the Bartha genome, only three viral gene products are essential for neurovirulence. These three proteins are glycoprotein E (gE), glycoprotein I (gl) and US9 (US9) phosphoprotein. We have developed a mouse flank infection model of PRV pathogenesis that provides a variety of virulence phenotypes never before available for detailed molecular analysis. We have demonstrated that Becker infected mice die rapidly and self-mutilate in response to a virally induced stimulus at the site of inoculation to produce severe flank skin lesions. The rapidity with which these animals die and the clinical signs they exhibit suggest that they succumb to an overwhelming systemic inflammatory response mediated by the innate immune system. PRV-Bartha infected animals live more than twice as long as Becker infected animals, do not self-mutilate and do not develop skin lesions. However, these animals display severe CMS abnormalities. This is suggestive that, because the animals do not mount a toxic systemic inflammatory response, the virus is able to travel to the brain and replicate to induce fatal encephalitis. We hypothesize that the key viral proteins essential for induction of the host immune and nervous system responses to PRV are glycoprotein E, glycoprotein I and US9 protein.
| Reynolds, Ashley E; Enquist, L W (2006) Biological interactions between herpesviruses and cyclooxygenase enzymes. Rev Med Virol 16:393-403 |
| Pomeranz, Lisa E; Reynolds, Ashley E; Hengartner, Christoph J (2005) Molecular biology of pseudorabies virus: impact on neurovirology and veterinary medicine. Microbiol Mol Biol Rev 69:462-500 |
