Virus-host interactions governing alpha-herpesvirus genome delivery and neuroinvasion

项目总结 神经侵袭性疱疹病毒从感觉神经元传播到眼睛、大脑或从母亲传播到 新生儿，是发病率和死亡率的重要原因。单纯疱疹病毒1型(HSV1)和 伪狂犬病病毒(PRV)是哺乳动物两个属的代表性成员 神经侵袭性疱疹病毒(单纯疱疹病毒和水痘病毒)。这些病毒依赖于 扩散到神经系统建立终生潜伏感染，但对 这一显著特征背后的神经侵袭机制。我们建议研究这种病毒 神经入侵机制的目的是：(I)破译这些病毒如何入侵神经系统， (Ii)了解这些病毒逃避的神经感染的内在障碍，以及(Iii)产生和 将缺乏神经侵袭性的病毒鉴定为潜在的疫苗和重组载体。 这些研究旨在确定促进病毒基因组传递的病毒与细胞之间的相互作用 到非神经元和神经元细胞的细胞核，以及相应的固有防御 大多数病原体都在海湾里。我们包括初步数据表明，这一开创性的合作 这项研究具有深远的医学和生物学意义。

PROJECT SUMMARY 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 vaccines and recombinant vectors. These studies are designed to identify the virus-cellular interactions that promote virus genome delivery to the nuclei of non-neuronal and neuronal cells, and the corresponding intrinsic 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.