INVOLVEMENT OF AMINOPEPTIDASE-N (CD13) IN INFECTION OF HUMAN NEURAL CELLS BY HUMAN CORONAVIRUS 229E

Attachment to a cell surface receptor can be a major determinant of vi rus tropism. Previous studies have shown that human respiratory corona virus HCV-229E uses human aminopeptidase N (hAPN [CD13]) as its cellul ar receptor for infection of lung fibroblasts. Although human coronavi ruses are recognized respiratory pathogens, occasional reports have su ggested their possible neurotropism. We have previously shown that hum an neural cells, including glial cells in primary cultures, are suscep tible to human coronavirus infection in vitro (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). However, th e only reported expression of hAPN in the nervous system is at the lev el of nerve synapses. Therefore,,ve asked whether hAPN is utilized as a cellular receptor for infection of these human neural cell lines. Us ing how cytometry, we were able to show the expression of hAPN on the surfaces of various human neuronal and glial cell lines that are susce ptible to HCV-229E infection. An hAPN-specific monoclonal antibody (WM 15), but not control antibody, inhibited the attachment of radiolabele d 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,vas observed. Furthermore, the presence of W M15 inhibited virus infection of these cell lines, as detected by indi rect immunofluorescence. These results indicate that hAPN (CD13) is ex pressed on neuronal and glial cell lines in vitro and serves as the re ceptor for infection by HCV-229E. This further strengthens the neurotr opic potential of this human respiratory virus.