Tirabassi R S, Townley R A, Eldridge M G, Enquist L W
Department of Molecular Biology, Princeton University, NJ 08544, USA.
Neurosci Biobehav Rev. 1998 Oct;22(6):709-20. doi: 10.1016/s0149-7634(98)00009-8.
Pseudorabies virus (PRV) is a herpesvirus in the subfamily alphaherpesvirinae (the alpha herpesviruses). After primary infection at mucosal surfaces, PRV infects the peripheral nervous system in its natural host (swine) with occasional invasion of the central nervous system. When other hosts (including cows and rodents) are infected, the infection almost always gives rise to fatal disease in the CNS as a result of infection of peripheral neurons and subsequent spread to the brain. Part of the ability to cause fatal CNS disease can be attributed to a viral glycoprotein called gE. Viruses lacking gE are thought to be less virulent because they do not spread efficiently from cell to cell. Based on a set of gE mutations we have constructed, we suggest that these two phenotypes of cell-cell spread and virulence reflect separate functions of the gE protein. In this report, we show that viruses carrying these new gE mutations have marked reduction in virulence, yet spread efficiently in defined neural circuits in the rat brain. As such, they offer new insight and opportunities for understanding of viral disease and host response to injury, as well as in the construction of viral tracers of neuronal connections.
伪狂犬病病毒（PRV）是α疱疹病毒亚科（α疱疹病毒）中的一种疱疹病毒。在黏膜表面初次感染后，PRV在其自然宿主（猪）中感染外周神经系统，偶尔也会侵入中枢神经系统。当其他宿主（包括牛和啮齿动物）被感染时，由于外周神经元感染并随后扩散至大脑，感染几乎总会导致中枢神经系统的致命疾病。导致致命中枢神经系统疾病的部分能力可归因于一种名为gE的病毒糖蛋白。缺乏gE的病毒被认为毒性较低，因为它们不能在细胞间有效传播。基于我们构建的一组gE突变，我们认为细胞间传播和毒力这两种表型反映了gE蛋白的不同功能。在本报告中，我们表明携带这些新gE突变的病毒毒力显著降低，但能在大鼠大脑特定的神经回路中有效传播。因此，它们为理解病毒性疾病和宿主对损伤的反应，以及构建神经元连接的病毒示踪剂提供了新的见解和机会。
