Ginsberg H S, Horswood R L, Chanock R M, Prince G A
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Proc Natl Acad Sci U S A. 1990 Aug;87(16):6191-5. doi: 10.1073/pnas.87.16.6191.
Intranasal inoculation of type 5 adenovirus into the cotton rat Sigmodon hispidus produces a pneumonia pathologically similar to that in humans, and it, therefore, provides an excellent animal model to investigate the pathogenesis of this disease. The goal of this study was to test the hypothesis that accumulation of viral structural proteins is responsible for a major portion of the cell-damage-producing disease. Since viral DNA replication is essential for synthesis of the viral structural proteins, which are products of late genes, the hypothesis was tested using mutants defective in genes required for DNA synthesis. Most experiments were done with the conditionally lethal temperature-sensitive (ts) mutant H5ts125, which contains a mutation in the early region 2A (E2A) gene encoding the DNA-binding protein. The data show that infection with 1 x 10(9.0) plaque-forming units of H5ts125 induced a pneumonia that was as extensive and qualitatively the same as that after wild-type adenovirus type 5 infection, although H5ts125 did not replicate to produce infectious virus. When cotton rats were infected with 1 x 10(8.0) plaque-forming units of wild-type adenovirus type 5 or H5ts125, the pneumonias that followed were pathologically similar; in the latter phases, however, wild-type virus produced slightly more extensive pneumonia than did H5ts125, probably because its replication permitted infection of more susceptible cells.
将5型腺病毒经鼻内接种到棉鼠（Sigmodon hispidus）体内会引发一种在病理上与人类肺炎相似的疾病，因此，它为研究这种疾病的发病机制提供了一个极佳的动物模型。本研究的目的是检验以下假设：病毒结构蛋白的积累是造成产生细胞损伤疾病的主要原因。由于病毒DNA复制对于病毒结构蛋白的合成至关重要，而病毒结构蛋白是晚期基因的产物，因此使用DNA合成所需基因存在缺陷的突变体来检验这一假设。大多数实验是用条件致死性温度敏感（ts）突变体H5ts125进行的，该突变体在编码DNA结合蛋白的早期区域2A（E2A）基因中存在突变。数据表明，用1×10(9.0) 个噬斑形成单位（pfu）的H5ts125感染会诱发一种肺炎，其范围和性质与野生型5型腺病毒感染后的肺炎相同，尽管H5ts125不会复制产生感染性病毒。当棉鼠用1×10(8.0) 个噬斑形成单位的野生型5型腺病毒或H�ts125感染时，随后发生的肺炎在病理上相似；然而，在后期，野生型病毒产生的肺炎比H5ts125略广泛，可能是因为其复制允许感染更多易感细胞。
