Acute and persistent infection of human neural cell lines by human coronavirus OC43
Acute and persistent infection of human neural cell lines by human coronavirus OC43
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DOI：
10.1128/jvi.73.4.3338-3350.1999
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发表时间：
1999-04-01
影响因子：
5.4
通讯作者：
Talbot, PJ
中科院分区：
文献类型：
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作者：
Arbour, N;Côté, G;Talbot, PJ
人类冠状病毒（HuCV）是公认的呼吸道病原体。不同实验室积累的数据表明它们具有神经营养潜力。例如，人星形胶质细胞和小胶质细胞的原代培养物显示对HuCV的OC43株感染敏感(A.Bonavia，N.Arbour，V.W.Yong，和P.J.Talbot，J.Virol.71：800-806，1997)。我们推测 HuCV 的神经趋向性将导致在中枢神经系统内持续存在，正如在鼠冠状病毒中观察到的那样。作为验证我们假设的第一步，我们表征了各种人类神经细胞系对 HuCV-OC43 感染的敏感性。在急性和持续感染期间监测病毒抗原、感染性病毒后代和病毒RNA。星形细胞瘤细胞系 U-87 MG、U-373 MG 和 GL-15，以及神经母细胞瘤 SK-N-SH、神经胶质瘤 H4、少突胶质细胞 MO3.13 和 CHME-5 永生化胎儿小胶质细胞系，都对 HuCV-OC43 的急性感染敏感。在 U-87 MG、U-373 MG、MO3.13 和 H4 细胞系持续 HuCV-OC43 感染（类似于培养 130 天）期间，观察到病毒抗原和 RNA 以及感染性病毒颗粒的释放。将培养130天后获得的编码推定高变病毒S1基因片段的RNA的核苷酸序列与初始病毒输入的序列进行比较。在所有持续感染的细胞系中都观察到导致氨基酸变化的点突变。此外，在持续感染的 H4 细胞中也观察到框内缺失。在一些分子克隆中观察到一些点突变，但不是全部，这表明在 H4、U-87 MG 和 MO3.13 细胞系持续感染期间病毒群体的进化和病毒准种的出现。这些结果与 HuCV-OC43 在人类神经系统细胞中的潜在持久性一致，并伴随着感染性病毒颗粒的产生和病毒基因组 RNA 的分子变异。
Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated by different laboratories suggest their neurotropic potential. For example, primary cultures of human astrocytes and microglia were shown to be susceptible to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). We speculate that the neurotropism of HuCV will lead to persistence within the central nervous system, as was observed for murine coronaviruses. As a first step in the verification of our hypothesis, we have characterized the susceptibility of various human neural cell lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal microglial cell lines, mere all susceptible to an acute infection by HuCV-OC43. Viral antigen and RNA and release of infectious virions were observed during persistent HuCV-OC43 infections (similar to 130 days of culture) of U-87 MG, U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the putatively hypervariable viral S1 gene fragment obtained after 130 days of culture were compared to that of initial virus input. Point mutations leading to amino acid changes were observed in all persistently infected cell lines. Moreover, an in-frame deletion was also observed in persistently infected H4 cells. Some point mutations were observed in some molecular clones but not all, suggesting evolution of the viral population and the emergence of viral quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines. These results are consistent with the potential persistence of HuCV-OC43 in cells of the human nervous system, accompanied by the production of infectious virions and molecular variation of viral genomic RNA.