Mattila R K, Harila K, Kangas S M, Paavilainen H, Heape A M, Mohr I J, Hukkanen V
Research Center for Biomedicine, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland.
Department of Virology, University of Turku, Turku, Finland.
J Gen Virol. 2015 Aug;96(8):2304-2313. doi: 10.1099/vir.0.000138. Epub 2015 Apr 8.
After a primary lytic infection at the epithelia, herpes simplex virus type 1 (HSV-1) enters the innervating sensory neurons and translocates to the nucleus, where it establishes a quiescent latent infection. Periodically, the virus can reactivate and the progeny viruses spread back to the epithelium. Here, we introduce an embryonic mouse dorsal root ganglion (DRG) culture system, which can be used to study the mechanisms that control the establishment, maintenance and reactivation from latency. Use of acyclovir is not necessary in our model. We examined different phases of the HSV-1 life cycle in DRG neurons, and showed that WT HSV-1 could establish both lytic and latent form of infection in the cells. After reactivating stimulus, the WT viruses showed all markers of true reactivation. In addition, we showed that deletion of the γ(1)34.5 gene rendered the virus incapable of reactivation, even though the virus was clearly able to replicate and persist in a quiescent form in the DRG neurons.
在1型单纯疱疹病毒（HSV-1）在上皮细胞进行原发性裂解感染后，它进入支配感觉神经元并转移至细胞核，在那里建立静止的潜伏感染。病毒可周期性地重新激活，子代病毒再扩散回上皮细胞。在此，我们介绍一种胚胎小鼠背根神经节（DRG）培养系统，可用于研究控制潜伏期建立、维持和重新激活的机制。在我们的模型中无需使用阿昔洛韦。我们研究了DRG神经元中HSV-1生命周期的不同阶段，结果表明野生型HSV-1能够在细胞中建立裂解性和潜伏性感染形式。在重新激活刺激后，野生型病毒表现出真正重新激活的所有标志物。此外，我们还表明，γ(1)34.5基因的缺失使病毒无法重新激活，尽管该病毒显然能够在DRG神经元中以静止形式复制并持续存在。
