ROLE OF EARLY REGION-3 (E3) IN PATHOGENESIS OF ADENOVIRUS DISEASE
ROLE OF EARLY REGION-3 (E3) IN PATHOGENESIS OF ADENOVIRUS DISEASE
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DOI：
10.1073/pnas.86.10.3823
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
PRINCE, GA
中科院分区：
文献类型：
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作者：
GINSBERG, HS;LUNDHOLMBEAUCHAMP, U;PRINCE, GA
棉鼠 Sigmodon hispidus 提供了腺病毒肺炎的动物模型，可以研究产生该疾病所需的病毒基因产物以及影响损害的分子机制。这项研究的目的是检验以下假设：腺病毒基因组的早期区域 2 (E3) 在病毒疾病过程的发病机制中发挥着关键作用，尽管其基因产物都不是其复制所必需的。 E3区大量缺失的突变体（即H2d1801和H5d1327）在棉鼠肺部像野生型病毒一样复制，但淋巴细胞和巨噬细胞/单核细胞炎症反应显着增强。含有消除19-kDa糖蛋白产生的突变的病毒具有与H2d1801和H5d1327相同的效果。然而，其他 E3 开放阅读框（其中一些编码已知蛋白质）缺失的突变体在致病特性上与野生型病毒没有区别。 19-kDa 糖蛋白显着降低受感染细胞表面 I 类主要组织相容性复合物抗原的表达。在那些具有增加的致病作用的突变体和那些失去了减少I类主要组织相容性复合物抗原向感染细胞表面转运的能力的突变体（即所有突变体都不能表达19-kDa糖蛋白）之间发现了完全相关性。 H5sub304 在 E3B 区域有 83.2 至 85.1 个图谱单位的缺失，并表达 19-kDa 糖蛋白，它不会增加肺炎的程度，但会质性地改变炎症反应，因为多形核白细胞的积累数量增加，通常聚集在小病灶中。
The cotton rat Sigmodon hispidus has provided an animal model of adenovirus pneumonia that permits investigation of the viral gene products required to produce the disease and the molecular mechanisms effecting the damage. This study was carried out to test the hypothesis that early region 2 (E3) of the adenovirus genome plays a critical role in pathogenesis of the virus''s disease process even though none of its gene products are essential for its replication. Mutants whose E3 region is largely deleted (i.e., H2d1801 and H5d1327) replicated like wild-type virus in the cotton rats'' lungs, but the lymphocyte and macrophage/monocyte inflammatory response was markedly increased. Viruses containing mutations that ablated production of the 19-kDa glycoprotein had the same effect as H2dl801 and H5dl327. However, mutants with deletions in the other E3 open reading frames, some of which encode known proteins, did not differ from wild-type virus in their pathogenic properties. The 19-kDa glycoprotein markedly reduces expression of the class I major histocompatibility complex antigens on the surface of infected cells. A complete correlation was found between those mutants that had increased pathogenic effects and those that lost the ability to reduce transport of the class I major histocompatibility complex antigens to surface of infected cells (i.e., all mutants unable to express the 19-kDa glycoprotein). H5sub304, which has a deletion between 83.2 and 85.1 map units in the E3B region and expresses the 19-kDa glycoprotein, did not increase the extent of pneumonia but qualtiatively changed that inflammatory response in that increased numbers of polymorphonuclear leukocytes accumulated, often in small foci.