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CD13 (human aminopeptidase N) mediates human cytomegalovirus infection
C Söderberg1, T D Giugni, J A Zaia
1Department of Clinical Immunology, NOVUM, Karolinska Institute at Huddinge Hospital, Stockholm, Sweden.
Abstract:
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.
Insights
Human cytomegalovirus (HCMV) uses CD13 to infect cells by increasing viral binding. However, the enzyme activity of CD13 is not required for this HCMV infection process.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human cytomegalovirus (HCMV) infection mechanisms, particularly early events like cell entry, remain incompletely understood.
- CD13, a metalloprotease also known as human aminopeptidase N, is expressed on cells susceptible to HCMV infection in vitro.
Purpose of the Study:
- To investigate the role of human CD13 in HCMV infection.
- To determine if CD13 mediates HCMV attachment, entry, or other early infection processes.
Main Methods:
- Utilized antibodies against CD13 to assess their impact on HCMV infection and virion binding.
- Employed aminopeptidase inhibitors to evaluate their effect on HCMV infection.
- Transfected HCMV-resistant murine fibroblasts with human CD13 cDNA to assess susceptibility to HCMV.
- Created and tested transfectants with a mutant CD13 lacking an active aminopeptidase site.
Main Results:
- Antibodies against CD13 inhibited HCMV infection and blocked HCMV virion binding to susceptible cells.
- Aminopeptidase inhibitors reduced HCMV infection rates.
- Murine fibroblasts expressing human CD13 showed increased HCMV binding and susceptibility to infection.
- Transfection with a mutant CD13, lacking the active site, did not restore HCMV susceptibility, despite increased binding.
Conclusions:
- Human CD13 plays a significant role in mediating HCMV infection.
- CD13 facilitates HCMV infection primarily by enhancing viral binding to cells.
- The enzymatic activity of CD13's active site is not essential for HCMV infection, suggesting a structural or binding-dependent role.