Spread of neuroinvasive herpesviruses from sensory neurons to the eye, brain or from mother to newborn, are significant causes of morbidity and mortality. Herpes simplex virus type 1 (HSV1) and pseudorabies virus (PRV) are representative members of the two genuses of mammalian neuroinvasive herpesviruses (simplexviruses & varicelloviruses). These viruses are dependent upon spread to the nervous system to establish life-long latent infections, yet very little is known regarding the neuroinvasive mechanism that underlies this remarkable trait. We propose to study the virus neuroinvasive machinery with the intent to: (i) decipher how these viruses invade the nervous system, (ii) understand the intrinsic barriers to neural infection that these viruses evade, and (iii) produce and characterize viruses lacking the neuroinvasive property as potential vaccine tools. These studies are designed to decode the virus tactics used to establish neural infections and our corresponding nervous system's defenses that keep most pathogens at bay. We include preliminary data demonstrating that this path-breaking collaborative study has far-reaching medical and biological implications.
Neuroinvasive herpesviruses are the causative agents of a number of severe diseases including encephalitis, shingles, neonatal infections and herpes keratitis. The goal of these studies it to develop a working understanding of the neuroinvasive property of these viruses, with the expectation that the research will lead to new resources in the continuing effort to develop antivirals and vaccines.
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