Morrison L A, Knipe D M
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Virology. 1996 Jun 15;220(2):402-13. doi: 10.1006/viro.1996.0328.
We have investigated the mechanisms by which subcutaneous immunization of mice with a replication-defective mutant of herpes simplex virus 1 protects against infection of the eye and latent infection of the trigeminal ganglion following corneal challenge. First, we have shown that immunization reduces the number of trigeminal ganglion neurons in challenged animals that express the latency-associated transcript. This indicates that the reduction in the incidence of latent infection by challenge virus is likely due to immune mechanisms and not saturation of the potential sites of latent infection by the immunizing mutant virus itself. Second, the duration of protective immunity against acute infection, keratitis, and latent infection was similar in mice immunized with replication-defective or -competent virus; thus, the replication-defective mutant virus is able to induce durable immunity apparently without spread in the host. Third, although the mutant virus showed no evidence of replication in vivo, it was present in footpad tissue in an infectious form for several days. This surprising observation raises the possibility that continued infection events by input virus over an extended period of time may have a boosting effect on the developing immune response which could explain, at least in part, the capacity of these replication-defective mutant viruses to elicit a robust and durable immunity despite their inability to spread within the host.
我们研究了用1型单纯疱疹病毒复制缺陷型突变体对小鼠进行皮下免疫，从而在角膜激发后预防眼部感染和三叉神经节潜伏感染的机制。首先，我们发现免疫可减少受激发动物中表达潜伏相关转录本的三叉神经节神经元数量。这表明激发病毒导致的潜伏感染发生率降低可能是由于免疫机制，而非免疫突变病毒本身使潜伏感染潜在位点饱和所致。其次，用复制缺陷型或有复制能力的病毒免疫的小鼠，针对急性感染、角膜炎和潜伏感染的保护性免疫持续时间相似；因此，复制缺陷型突变病毒显然能够在不于宿主体内传播的情况下诱导持久免疫。第三，尽管突变病毒在体内未显示出复制迹象，但它以感染性形式在足垫组织中存在了数天。这一惊人发现增加了一种可能性，即输入病毒在较长时间内持续发生的感染事件可能对正在发育的免疫反应有增强作用，这至少可以部分解释这些复制缺陷型突变病毒尽管无法在宿主体内传播却仍能引发强大而持久免疫的能力。
