Banfield B W, Yap G S, Knapp A C, Enquist L W
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
J Virol. 1998 Jun;72(6):4580-8. doi: 10.1128/JVI.72.6.4580-4588.1998.
We describe use of developing chicken embryos as a model to study neuronal spread and virulence of pseudorabies virus (PRV). At embryonic day 12, beta-galactosidase-expressing PRV strains were injected into the vitreous humor of one eye, and virus replication and spread from the eye to the brain were measured by beta-galactosidase activity and the recovery of infectious virus from tissues. The wild-type PRV strain, Becker, replicated in the eye and then spread to the brain, causing extensive pathology characterized by edema, hemorrhage, and necrosis that localized to virally infected tissue. The attenuated vaccine strain, Bartha, replicated in the eye and spread throughout specific regions of the brain, producing little to no overt pathology. Becker mutants lacking membrane proteins gE or gI replicated in the eye and were able to spread to the brain efficiently. The pathology associated with replication of these mutants in the brain was intermediate to that induced by Becker or Bartha. Mixed infection of a gE deletion mutant and a gI deletion mutant restored the pathogenic phenotype to wild-type levels. These data indicate that the replication of virus in embryonic brain tissue is not sufficient to induce the characteristic pathological response and that the gE and gI gene products actively affect pathological responses in the developing chicken brain.
我们描述了利用发育中的鸡胚作为模型来研究伪狂犬病病毒（PRV）的神经元传播和毒力。在胚胎第12天，将表达β-半乳糖苷酶的PRV毒株注射到一只眼睛的玻璃体内，通过β-半乳糖苷酶活性以及从组织中回收感染性病毒来测量病毒的复制以及从眼睛向大脑的传播。野生型PRV毒株Becker在眼睛中复制，然后扩散到大脑，导致以水肿、出血和坏死为特征的广泛病理变化，这些病变局限于病毒感染的组织。减毒疫苗毒株Bartha在眼睛中复制并扩散到大脑的特定区域，几乎没有产生明显的病理变化。缺乏膜蛋白gE或gI的Becker突变体在眼睛中复制，并能够有效地扩散到大脑。与这些突变体在大脑中复制相关的病理变化介于Becker或Bartha诱导的病理变化之间。gE缺失突变体和gI缺失突变体的混合感染将致病表型恢复到野生型水平。这些数据表明，病毒在胚胎脑组织中的复制不足以诱导特征性的病理反应，并且gE和gI基因产物积极影响发育中的鸡脑中的病理反应。
