CD13 (human aminopeptidase N) mediates human cytomegalovirus infection

Human cytomegalovirus (HCMV) infects cells by a series of processes including attachment, penetration via fusion of the envelope with the plasma membrane, and transport of the viral DNA to the nucleus. The details of the early events of HCMV Infection are poorly understood. We have recently reported that CD13, human Aminopeptidase N, a metalloprotease, is present on blood cells susceptible in vitro to HCMV Infection (C. Söderberg, S. Larsson, S. Bergstedt-Lindqvist, and E. Möller, J. Virol. 67:3166-3175, 1993). Here we report that human CD13 is involved in HCMV Infection. Antibodies directed against human CD13 not only inhibit Infection but also block binding of HCMV virions to susceptible cells. Compounds known to inhibit Aminopeptidase activity block HCMV Infection. HCMV-resistant murine fibroblasts have heightened susceptibility to HCMV Infection after transfection with complementary DNA encoding 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 mutant CD13, lacking a portion of the Aminopeptidase active site, remained susceptible to HCMV Infection. Thus, human CD13 appears to mediate HCMV Infection by a process that increases binding, but its enzymatic domain is not necessary for Infection.