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. 1993 Nov;67(11):6576–6585. doi: 10.1128/jvi.67.11.6576-6585.1993

CD13 (human aminopeptidase N) mediates human cytomegalovirus infection.

C Söderberg 1, T D Giugni 1, J A Zaia 1, S Larsson 1, J M Wahlberg 1, E Möller 1
PMCID: PMC238095  PMID: 8105105

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.

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Selected References

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  1. Adlish J. D., Lahijani R. S., St Jeor S. C. Identification of a putative cell receptor for human cytomegalovirus. Virology. 1990 Jun;176(2):337–345. doi: 10.1016/0042-6822(90)90003-a. [DOI] [PubMed] [Google Scholar]
  2. Ashmun R. A., Look A. T. Metalloprotease activity of CD13/aminopeptidase N on the surface of human myeloid cells. Blood. 1990 Jan 15;75(2):462–469. [PubMed] [Google Scholar]
  3. Ashmun R. A., Shapiro L. H., Look A. T. Deletion of the zinc-binding motif of CD13/aminopeptidase N molecules results in loss of epitopes that mediate binding of inhibitory antibodies. Blood. 1992 Jun 15;79(12):3344–3349. [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Compton T., Nowlin D. M., Cooper N. R. Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate. Virology. 1993 Apr;193(2):834–841. doi: 10.1006/viro.1993.1192. [DOI] [PubMed] [Google Scholar]
  6. Delmas B., Gelfi J., L'Haridon R., Vogel L. K., Sjöström H., Norén O., Laude H. Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature. 1992 Jun 4;357(6377):417–420. doi: 10.1038/357417a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Favaloro E. J., Bradstock K. F., Kabral A., Grimsley P., Zowtyj H., Zola H. Further characterization of human myeloid antigens (gp160,95; gp150; gp67): investigation of epitopic heterogeneity and non-haemopoietic distribution using panels of monoclonal antibodies belonging to CD-11b, CD-13 and CD-33. Br J Haematol. 1988 Jun;69(2):163–171. doi: 10.1111/j.1365-2141.1988.tb07618.x. [DOI] [PubMed] [Google Scholar]
  8. Fingeroth J. D., Weis J. J., Tedder T. F., Strominger J. L., Biro P. A., Fearon D. T. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510–4514. doi: 10.1073/pnas.81.14.4510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Greve J. M., Davis G., Meyer A. M., Forte C. P., Yost S. C., Marlor C. W., Kamarck M. E., McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839–847. doi: 10.1016/0092-8674(89)90688-0. [DOI] [PubMed] [Google Scholar]
  10. Griffiths P. D., Grundy J. E. Molecular biology and immunology of cytomegalovirus. Biochem J. 1987 Jan 15;241(2):313–324. doi: 10.1042/bj2410313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grundy J. E., McKeating J. A., Ward P. J., Sanderson A. R., Griffiths P. D. Beta 2 microglobulin enhances the infectivity of cytomegalovirus and when bound to the virus enables class I HLA molecules to be used as a virus receptor. J Gen Virol. 1987 Mar;68(Pt 3):793–803. doi: 10.1099/0022-1317-68-3-793. [DOI] [PubMed] [Google Scholar]
  12. Jacobson M. A., Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med. 1988 Apr;108(4):585–594. doi: 10.7326/0003-4819-108-4-585. [DOI] [PubMed] [Google Scholar]
  13. Kari B., Gehrz R. A human cytomegalovirus glycoprotein complex designated gC-II is a major heparin-binding component of the envelope. J Virol. 1992 Mar;66(3):1761–1764. doi: 10.1128/jvi.66.3.1761-1764.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Keay S., Baldwin B. Anti-idiotype antibodies that mimic gp86 of human cytomegalovirus inhibit viral fusion but not attachment. J Virol. 1991 Sep;65(9):5124–5128. doi: 10.1128/jvi.65.9.5124-5128.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Keay S., Merigan T. C., Rasmussen L. Identification of cell surface receptors for the 86-kilodalton glycoprotein of human cytomegalovirus. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10100–10103. doi: 10.1073/pnas.86.24.10100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Käriäinen L., Simons K., von Bonsdorff C. H. Studies in subviral components of Semliki Forest virus. Ann Med Exp Biol Fenn. 1969;47(4):235–248. [PubMed] [Google Scholar]
  17. Lentz T. L. The recognition event between virus and host cell receptor: a target for antiviral agents. J Gen Virol. 1990 Apr;71(Pt 4):751–766. doi: 10.1099/0022-1317-71-4-751. [DOI] [PubMed] [Google Scholar]
  18. Look A. T., Ashmun R. A., Shapiro L. H., Peiper S. C. Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. J Clin Invest. 1989 Apr;83(4):1299–1307. doi: 10.1172/JCI114015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nowlin D. M., Cooper N. R., Compton T. Expression of a human cytomegalovirus receptor correlates with infectibility of cells. J Virol. 1991 Jun;65(6):3114–3121. doi: 10.1128/jvi.65.6.3114-3121.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Paulson J. C., Sadler J. E., Hill R. L. Restoration of specific myxovirus receptors to asialoerythrocytes by incorporation of sialic acid with pure sialyltransferases. J Biol Chem. 1979 Mar 25;254(6):2120–2124. [PubMed] [Google Scholar]
  21. Rich D. H., Moon B. J., Harbeson S. Inhibition of aminopeptidases by amastatin and bestatin derivatives. Effect of inhibitor structure on slow-binding processes. J Med Chem. 1984 Apr;27(4):417–422. doi: 10.1021/jm00370a001. [DOI] [PubMed] [Google Scholar]
  22. Rubin R. H., Cosimi A. B., Tolkoff-Rubin N. E., Russell P. S., Hirsch M. S. Infectious disease syndromes attributable to cytomegalovirus and their significance among renal transplant recipients. Transplantation. 1977 Dec;24(6):458–464. doi: 10.1097/00007890-197712000-00010. [DOI] [PubMed] [Google Scholar]
  23. Schlegel R., Tralka T. S., Willingham M. C., Pastan I. Inhibition of VSV binding and infectivity by phosphatidylserine: is phosphatidylserine a VSV-binding site? Cell. 1983 Feb;32(2):639–646. doi: 10.1016/0092-8674(83)90483-x. [DOI] [PubMed] [Google Scholar]
  24. Semenza G. Anchoring and biosynthesis of stalked brush border membrane proteins: glycosidases and peptidases of enterocytes and renal tubuli. Annu Rev Cell Biol. 1986;2:255–313. doi: 10.1146/annurev.cb.02.110186.001351. [DOI] [PubMed] [Google Scholar]
  25. Spaete R. R., Mocarski E. S. Insertion and deletion mutagenesis of the human cytomegalovirus genome. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7213–7217. doi: 10.1073/pnas.84.20.7213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Swenson P. D., Kaplan M. H. Rapid detection of cytomegalovirus in cell culture by indirect immunoperoxidase staining with monoclonal antibody to an early nuclear antigen. J Clin Microbiol. 1985 May;21(5):669–673. doi: 10.1128/jcm.21.5.669-673.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Söderberg C., Larsson S., Bergstedt-Lindqvist S., Möller E. Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection. J Virol. 1993 Jun;67(6):3166–3175. doi: 10.1128/jvi.67.6.3166-3175.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Taylor H. P., Cooper N. R. Human cytomegalovirus binding to fibroblasts is receptor mediated. J Virol. 1989 Sep;63(9):3991–3998. doi: 10.1128/jvi.63.9.3991-3998.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Taylor H. P., Cooper N. R. The human cytomegalovirus receptor on fibroblasts is a 30-kilodalton membrane protein. J Virol. 1990 Jun;64(6):2484–2490. doi: 10.1128/jvi.64.6.2484-2490.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Umezawa H., Aoyagi T., Tanaka T., Suda H., Okuyama A., Naganawa H., Hamada M., Takeuchi T. Production of actinonin, an inhibitor of aminopeptidase M, by actinomycetes. J Antibiot (Tokyo) 1985 Nov;38(11):1629–1630. doi: 10.7164/antibiotics.38.1629. [DOI] [PubMed] [Google Scholar]
  31. Vallee B. L., Auld D. S. Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry. 1990 Jun 19;29(24):5647–5659. doi: 10.1021/bi00476a001. [DOI] [PubMed] [Google Scholar]
  32. Wentworth B. B., French L. Plaque assay of cytomegalovirus strains of human origin. Proc Soc Exp Biol Med. 1970 Nov;135(2):253–258. doi: 10.3181/00379727-135-35031. [DOI] [PubMed] [Google Scholar]
  33. Wilkes S. H., Prescott J. M. The slow, tight binding of bestatin and amastatin to aminopeptidases. J Biol Chem. 1985 Oct 25;260(24):13154–13162. [PubMed] [Google Scholar]
  34. WuDunn D., Spear P. G. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol. 1989 Jan;63(1):52–58. doi: 10.1128/jvi.63.1.52-58.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yeager C. L., Ashmun R. A., Williams R. K., Cardellichio C. B., Shapiro L. H., Look A. T., Holmes K. V. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992 Jun 4;357(6377):420–422. doi: 10.1038/357420a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zaia J. A. Viral infections associated with bone marrow transplantation. Hematol Oncol Clin North Am. 1990 Jun;4(3):603–623. [PubMed] [Google Scholar]

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