Lachance C, Arbour N, Cashman N R, Talbot P J
Laboratory of Neuroimmunovirology, Armand-Frappier Institute, University of Quebec, Laval, Quebec H7V 1B7.
J Virol. 1998 Aug;72(8):6511-9. doi: 10.1128/JVI.72.8.6511-6519.1998.
Attachment to a cell surface receptor can be a major determinant of virus tropism. Previous studies have shown that human respiratory coronavirus HCV-229E uses human aminopeptidase N (hAPN [CD13]) as its cellular receptor for infection of lung fibroblasts. Although human coronaviruses are recognized respiratory pathogens, occasional reports have suggested their possible neurotropism. We have previously shown that human neural cells, including glial cells in primary cultures, are susceptible to human coronavirus infection in vitro (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). However, the only reported expression of hAPN in the nervous system is at the level of nerve synapses. Therefore, we asked whether hAPN is utilized as a cellular receptor for infection of these human neural cell lines. Using flow cytometry, we were able to show the expression of hAPN on the surfaces of various human neuronal and glial cell lines that are susceptible to HCV-229E infection. An hAPN-specific monoclonal antibody (WM15), but not control antibody, inhibited the attachment of radiolabeled HCV-229E to astrocytic, neuronal, and oligodendrocytic cell lines. A correlation between the apparent amount of cell surface hAPN and the level of virus attachment was observed. Furthermore, the presence of WM15 inhibited virus infection of these cell lines, as detected by indirect immunofluorescence. These results indicate that hAPN (CD13) is expressed on neuronal and glial cell lines in vitro and serves as the receptor for infection by HCV-229E. This further strengthens the neurotropic potential of this human respiratory virus.
与细胞表面受体的结合可能是病毒嗜性的主要决定因素。先前的研究表明，人类呼吸道冠状病毒HCV - 229E利用人类氨肽酶N（hAPN [CD13]）作为其感染肺成纤维细胞的细胞受体。尽管人类冠状病毒是公认的呼吸道病原体，但偶尔有报道表明它们可能具有嗜神经性。我们之前已经表明，包括原代培养的神经胶质细胞在内的人类神经细胞在体外易受人类冠状病毒感染（A. 博纳维亚、N. 阿尔布尔、V. W. 勇和P. J. 塔尔博特，《病毒学杂志》71:800 - 806，1997年）。然而，hAPN在神经系统中唯一报道的表达是在神经突触水平。因此，我们询问hAPN是否被用作这些人类神经细胞系感染的细胞受体。通过流式细胞术，我们能够显示hAPN在各种易受HCV - 229E感染的人类神经元和神经胶质细胞系表面的表达。一种hAPN特异性单克隆抗体（WM15），而不是对照抗体，抑制了放射性标记的HCV - 229E与星形胶质细胞、神经元和少突胶质细胞系的结合。观察到细胞表面hAPN的表观量与病毒结合水平之间的相关性。此外，如通过间接免疫荧光检测到的，WM15的存在抑制了这些细胞系的病毒感染。这些结果表明，hAPN（CD13）在体外的神经元和神经胶质细胞系上表达，并作为HCV - 229E感染的受体。这进一步增强了这种人类呼吸道病毒的嗜神经潜力。
