ROLE OF EARLY GENES IN PATHOGENESIS OF ADENOVIRUS PNEUMONIA
ROLE OF EARLY GENES IN PATHOGENESIS OF ADENOVIRUS PNEUMONIA
复制标题
DOI：
10.1073/pnas.87.16.6191
复制
发表时间：
1990-08-01
影响因子：
11.1
通讯作者：
PRINCE, GA
中科院分区：
文献类型：
--
作者：
GINSBERG, HS;HORSWOOD, RL;PRINCE, GA
将5型腺病毒鼻内接种到棉鼠Sigmodon hispidus中可产生与人类病理相似的肺炎，因此为研究该疾病的发病机制提供了良好的动物模型。这项研究的目的是检验以下假设：病毒结构蛋白的积累是造成细胞损伤的疾病的主要原因。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 合成所需基因缺陷的突变体对该假设进行了检验。大多数实验都是使用条件致死温度敏感 (ts) 突变体 H5ts125 进行的，该突变体在编码 DNA 结合蛋白的早期 2A 区 (E2A) 基因中包含突变。数据显示，感染人数为1.次。 H5ts125 的 109.0 空斑形成单位诱导了肺炎，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。当棉鼠感染1次时。 108.0 野生型腺病毒 5 型或 H5ts125 空斑形成单位，随后出现的肺炎病理学相似；然而，在后期阶段，野生型病毒比 H5ts125 产生了稍微更广泛的肺炎，这可能是因为它的复制允许感染更易受影响的细胞。
Intranasal inoculation of type 5 adenovirus into the cotton rat Sigmodon hispidus produces a penumonia 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 .times. 109.0 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 .times. 108.0 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.