Hughes Scott A, Thaker Harshwardhan M, Racaniello Vincent R
Departments of Microbiology and Pathology, Columbia University College of Physicians and Surgeons, 701 West 168th Street, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15906-11. doi: 10.1073/pnas.2535934100. Epub 2003 Dec 12.
Echoviruses have been implicated in multiple human disease syndromes, including aseptic meningitis, paralysis, and heart disease, but no animal model is available for studying the pathogenesis of infection. Production of human integrin very late antigen 2, a receptor for echovirus type 1, in transgenic mice conferred susceptibility to viral infection. Intracerebral inoculation of newborn transgenic mice with echovirus leads to paralysis and wasting. No disease was observed in infected nontransgenic mice. In paralyzed mice significant damage was observed in the outer layers of the cerebrum, and numerous condensed neuronal nuclei were present. In contrast, intracerebral inoculation of adolescent (3- to 4-week-old) transgenic mice with echovirus type 1 did not lead to paralysis but an acute wasting phenotype and myocarditis. These findings establish human very late antigen 2 transgenic mice as a model for echovirus pathogenesis.
肠道病毒已被证实与多种人类疾病综合征有关,包括无菌性脑膜炎、瘫痪和心脏病,但目前尚无用于研究感染发病机制的动物模型。在转基因小鼠中产生人类整合素极晚期抗原2(1型肠道病毒的一种受体)可使其易受病毒感染。给新生转基因小鼠脑内接种肠道病毒会导致瘫痪和消瘦。在感染的非转基因小鼠中未观察到疾病。在瘫痪小鼠的大脑外层观察到明显损伤,并且存在大量浓缩的神经元细胞核。相比之下,给青春期(3至4周龄)的转基因小鼠脑内接种1型肠道病毒不会导致瘫痪,而是会出现急性消瘦表型和心肌炎。这些发现确立了人类极晚期抗原2转基因小鼠作为肠道病毒发病机制的模型。