Department Biology II, Division of Neurobiology, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany.
Department Biology II, Division of Neurobiology, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany; Institute of Zoology, University of Veterinary Medicine Hannover, 30599 Hannover, Germany.
Neuroscience. 2017 Dec 26;367:1-9. doi: 10.1016/j.neuroscience.2017.10.020. Epub 2017 Oct 22.
Pseudorabies virus (PRV), a neurovirulent α-herpesvirus, spreads between neurons at synaptic connections. PRV-infected neurons have been shown to exhibit functional deficits with the attenuated PRV152 Bartha strain negatively influencing neuronal functioning in in vitro model systems. However, the impact of this attenuated PRV152 Bartha strain on the native central nervous system has not been fully explored. Using a combination of in vivo stereotactic injections and post-hoc in vitro whole-cell recordings, we investigated the functional impact of PRV152 Bartha in the auditory system of juvenile Mongolian gerbils. The specificity of this virus strain to spread exclusively trans-synaptically in a retrograde fashion and the well-defined structure of the ascending auditory brainstem pathways allowed us to determine the physiological alterations in primary and secondary infected neurons. We find at primary and secondary infections sites, the inferior colliculus (IC) and dorsal nucleus of the lateral lemniscus respectively, a reduced excitability of infected cells. The loss of excitability is manifested by an increase in current threshold and a loss of action potential generation. The minor changes in the approximated passive membrane parameters induced by the infection cannot explain the full loss in excitability, indicating that channel densities and properties have changed. This impact on neuronal functioning might contribute to the lethal neurovirulent effects of PRV viruses as vital neuronal circuits might cease activity. Since the detrimental effects of the attenuated PRV152 Bartha strain are reduced compared to wild-type strains, it comprises an excellent tool to study the neuropathological mechanisms of viral infections.
伪狂犬病毒（PRV）是一种神经毒力的α-疱疹病毒，在突触连接的神经元之间传播。已经表明，感染 PRV 的神经元表现出功能缺陷，而减毒的 PRV152 Bartha 株在体外模型系统中对神经元功能产生负面影响。然而，这种减毒的 PRV152 Bartha 株对天然中枢神经系统的影响尚未得到充分探索。我们使用体内立体定向注射和事后体外全细胞记录的组合，研究了 PRV152 Bartha 在幼年沙鼠听觉系统中的功能影响。该病毒株特异性地以逆行的方式仅在突触间传播，以及上行听觉脑干通路的明确结构，使我们能够确定初级和次级感染神经元的生理变化。我们发现，在初级和次级感染部位，即下丘和外侧丘系背核，感染细胞的兴奋性降低。感染引起的近似被动膜参数的微小变化不能完全解释兴奋性的丧失，表明通道密度和特性发生了变化。这种对神经元功能的影响可能导致 PRV 病毒的致死性神经毒力效应，因为重要的神经元回路可能停止活动。由于与野生型毒株相比，减毒的 PRV152 Bartha 株的有害影响降低，因此它是研究病毒感染的神经病理学机制的绝佳工具。
