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人脊髓灰质炎病毒受体基因在转基因小鼠中的表达及脊髓灰质炎病毒的组织嗜性

Human poliovirus receptor gene expression and poliovirus tissue tropism in transgenic mice.

作者信息

Ren R, Racaniello V R

机构信息

Department of Microbiology, Columbia University College of Physicians & Surgeons, New York, New York 10032.

出版信息

J Virol. 1992 Jan;66(1):296-304. doi: 10.1128/JVI.66.1.296-304.1992.

Abstract

Expression of the human poliovirus receptor (PVR) in transgenic mice results in susceptibility to poliovirus infection. In the primate host, poliovirus infection is characterized by restricted tissue tropism. To determine the pattern of poliovirus tissue tropism in PVR transgenic mice, PVR gene expression and susceptibility to poliovirus infection were examined by in situ hybridization. PVR RNA is expressed in transgenic mice at high levels in neurons of the central and peripheral nervous system, developing T lymphocytes in the thymus, epithelial cells of Bowman's capsule and tubules in the kidney, alveolar cells in the lung, and endocrine cells in the adrenal cortex, and it is expressed at low levels in intestine, spleen, and skeletal muscle. After infection, poliovirus replication was detected only in neurons of the brain and spinal cord and in skeletal muscle. These results demonstrated that poliovirus tissue tropism is not governed solely by expression of the PVR gene nor by accessibility of cells to virus. Although transgenic mouse kidney tissue expressed poliovirus binding sites and was not a site of poliovirus replication, when cultivated in vitro, kidney cells developed susceptibility to infection. Identification of the changes in cultured kidney cells that permit poliovirus infection may provide information on the mechanism of poliovirus tissue tropism.

摘要

人脊髓灰质炎病毒受体(PVR)在转基因小鼠中的表达导致其对脊髓灰质炎病毒感染易感。在灵长类宿主中,脊髓灰质炎病毒感染的特征是具有受限的组织嗜性。为了确定PVR转基因小鼠中脊髓灰质炎病毒的组织嗜性模式,通过原位杂交检测了PVR基因表达和对脊髓灰质炎病毒感染的易感性。PVR RNA在转基因小鼠的中枢和外周神经系统神经元、胸腺中发育中的T淋巴细胞、肾小囊和肾小管的上皮细胞、肺中的肺泡细胞以及肾上腺皮质的内分泌细胞中高水平表达,而在肠、脾和骨骼肌中低水平表达。感染后,仅在脑和脊髓的神经元以及骨骼肌中检测到脊髓灰质炎病毒复制。这些结果表明,脊髓灰质炎病毒的组织嗜性并非仅由PVR基因的表达或细胞对病毒的可及性所决定。尽管转基因小鼠肾组织表达脊髓灰质炎病毒结合位点且不是脊髓灰质炎病毒复制的部位,但在体外培养时,肾细胞对感染产生了易感性。确定培养的肾细胞中允许脊髓灰质炎病毒感染的变化,可能会提供有关脊髓灰质炎病毒组织嗜性机制的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8014/238287/eb1a9684214b/jvirol00034-0318-a.jpg

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