Tan Cindy S E, Frederico Bruno, Stevenson Philip G
Sir Albert Sakzewski Virus Research Centre, Queensland Children's Medical Research Institute and Australian Infectious Disease Research Centre, University of Queensland and Royal Children's Hospital, Brisbane, Queensland 4029, Australia.
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 2QQ, UK.
J Virol Methods. 2014 Sep;206:105-14. doi: 10.1016/j.jviromet.2014.06.003. Epub 2014 Jun 10.
Herpesvirus transmission is sporadic, and infection may be asymptomatic or present only with secondary lesions after dissemination. Consequently host entry remains ill-understood. Experimental infections can be informative, but depend on inoculations that are inherently artificial and so need validation. Mice are a widely used experimental host. Alert mice inhale readily small (5 μl) liquid volumes, and Indian ink, luciferase or radiolabel delivered thus distributed to the nasopharynx and oropharynx. Murid Herpesvirus-4 or Herpes simplex virus type 1 delivered thus infected only the nose, arguing that host entry is nasal rather than oral. Marker or virus delivery to the lung depended on general anesthesia and a large inoculum volume (30 μl), and so needs further validation of physiological relevance. While lungs could be infected at lower doses than the upper respiratory tract, tracking experiments showed that nasal inocula pass mostly into the oropharynx, even when restricted to 1 μl. Thus, the relative inefficiency of experimental upper respiratory tract infection was attributable to limited liquid retention in this site. Nonetheless low volume intranasal delivery to alert mice provides a convenient way to model experimentally an apparently natural mode of herpesvirus host entry.
疱疹病毒传播具有散发性，感染可能无症状，或仅在病毒播散后出现继发性病变。因此，病毒进入宿主的机制仍未得到充分理解。实验性感染可能提供有用信息，但依赖于本质上人为的接种方式，因此需要验证。小鼠是广泛使用的实验宿主。警觉的小鼠很容易吸入少量（5微升）液体，通过这种方式递送的印度墨水、荧光素酶或放射性标记物会分布到鼻咽和口咽。通过这种方式递送的鼠疱疹病毒4型或单纯疱疹病毒1型仅感染鼻子，这表明病毒进入宿主的途径是经鼻而非经口。标记物或病毒递送至肺部依赖于全身麻醉和大剂量接种（30微升），因此需要进一步验证其生理相关性。虽然肺部能够以比上呼吸道更低的剂量被感染，但追踪实验表明，即使接种量限制在1微升，经鼻接种物大多会进入口咽。因此，实验性上呼吸道感染效率相对较低是由于该部位液体潴留有限。尽管如此，向警觉小鼠低容量鼻内递送为实验模拟疱疹病毒进入宿主的一种明显自然方式提供了便利途径。
