CD13 (HUMAN AMINOPEPTIDASE-N) MEDIATES HUMAN CYTOMEGALOVIRUS-INFECTION

Human cytomegalovirus (HCMV) infects cells by a series of processes in cluding attachment, penetration via fusion of the envelope with the pl asma membrane, and transport of the viral DNA to the nucleus. The deta ils of the early events of HCMV infection are poorly understood. We ha ve recently reported that CD13, human aminopeptidase N, a metalloprote ase, is present on blood cells susceptible in vitro to HCMV infection (C. Soderberg, S. Larsson, S. Bergstedt-Lindqvist, and E. Moller, J. V irol. 67:3166-3175, 1993). Here we report that human CD13 is involved in HCMV infection. Antibodies directed against human CD13 not only inh ibit infection but also block binding of HCMV virions to susceptible c ells. Compounds known to inhibit aminopeptidase activity block HCMV in fection. HCMV-resistant murine fibroblasts have heightened susceptibil ity to HCMV infection after transfection with complementary DNA encodi ng human CD13. A significant increase in binding of HCMV was observed in the CD13-expressing transfectants compared with neomycin-resistant control mouse cells. However, murine fibroblasts transfected with muta nt CD13, lacking a portion of the aminopeptidase active site, remained susceptible to HCMV infection. Thus, human CD13 appears to mediate HC MV infection by a process that increases binding, but its enzymatic do main is not necessary for infection.