Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63 Free

Abstract

Like severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus (HCoV)-NL63 employs angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry. SARS-CoV infection causes robust downregulation of cellular ACE2 expression levels and it has been suggested that the SARS-CoV effect on ACE2 is involved in the severity of disease. We investigated whether cellular ACE2 downregulation occurs at optimal replication conditions of HCoV-NL63 infection. The expression of the homologue of ACE2, the ACE protein not used as a receptor by HCoV-NL63, was measured as a control. A specific decrease for ACE2 protein level was observed when HCoV-NL63 was cultured at 34 °C. Culturing the virus at the suboptimal temperature of 37 °C resulted in low replication of the virus and the effect on ACE2 expression was lost. We conclude that the decline of ACE2 expression is dependent on the efficiency of HCoV-NL63 replication, and that HCoV-NL63 and SARS-CoV both affect cellular ACE2 expression during infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.043919-0
2012-09-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/9/1924.html?itemId=/content/journal/jgv/10.1099/vir.0.043919-0&mimeType=html&fmt=ahah

References

  1. Aiken C., Konner J., Landau N. R., Lenburg M. E., Trono D. 1994; Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76:853–864 [View Article][PubMed]
    [Google Scholar]
  2. Bradburne A. F., Bynoe M. L., Tyrrell D. A. 1967; Effects of a “new” human respiratory virus in volunteers. BMJ 3:767–769 [View Article][PubMed]
    [Google Scholar]
  3. Breiner K. M., Urban S., Glass B., Schaller H. 2001; Envelope protein-mediated down-regulation of hepatitis B virus receptor in infected hepatocytes. J Virol 75:143–150 [View Article][PubMed]
    [Google Scholar]
  4. Dijkman R., Mulder H. L., Rumping L., Kraaijvanger I., Deijs M., Jebbink M. F., Verschoor E. J., van der Hoek L. 2009; Seroconversion to HCoV-NL63 in rhesus macaques. Viruses 1:647–656 [View Article][PubMed]
    [Google Scholar]
  5. Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N., Donovan M., Woolf B., Robison K. other authors 2000; A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 87:E1–E9 [View Article][PubMed]
    [Google Scholar]
  6. Falsey A. R., McCann R. M., Hall W. J., Criddle M. M., Formica M. A., Wycoff D., Kolassa J. E. 1997; The “common cold” in frail older persons: impact of rhinovirus and coronavirus in a senior daycare center. J Am Geriatr Soc 45:706–711[PubMed] [CrossRef]
    [Google Scholar]
  7. Fouchier R. A., Kuiken T., Schutten M., van Amerongen G., van Doornum G. J., van den Hoogen B. G., Peiris M., Lim W., Stöhr K., Osterhaus A. D. 2003; Aetiology: Koch’s postulates fulfilled for SARS virus. Nature 423:240 [View Article][PubMed]
    [Google Scholar]
  8. Glowacka I., Bertram S., Herzog P., Pfefferle S., Steffen I., Muench M. O., Simmons G., Hofmann H., Kuri T. other authors 2010; Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. J Virol 84:1198–1205 [View Article][PubMed]
    [Google Scholar]
  9. Hofmann H., Pyrc K., van der Hoek L., Geier M., Berkhout B., Pöhlmann S. 2005; Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci U S A 102:7988–7993 [View Article][PubMed]
    [Google Scholar]
  10. Imai Y., Kuba K., Rao S., Huan Y., Guo F., Guan B., Yang P., Sarao R., Wada T. other authors 2005; Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436:112–116 [View Article][PubMed]
    [Google Scholar]
  11. Jia H. P., Look D. C., Tan P., Shi L., Hickey M., Gakhar L., Chappell M. C., Wohlford-Lenane C., McCray P. B. Jr 2009; Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol 297:L84–L96 [View Article][PubMed]
    [Google Scholar]
  12. Kraaijeveld C. A., Reed S. E., Macnaughton M. R. 1980; Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E. J Clin Microbiol 12:493–497[PubMed]
    [Google Scholar]
  13. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., Huan Y., Yang P., Zhang Y. other authors 2005; A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 11:875–879 [View Article][PubMed]
    [Google Scholar]
  14. Lambert D. W., Clarke N. E., Turner A. J. 2010; Not just angiotensinases: new roles for the angiotensin-converting enzymes. Cell Mol Life Sci 67:89–98 [View Article][PubMed]
    [Google Scholar]
  15. Li W., Moore M. J., Vasilieva N., Sui J., Wong S. K., Berne M. A., Somasundaran M., Sullivan J. L., Luzuriaga K. other authors 2003; Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454 [View Article][PubMed]
    [Google Scholar]
  16. Li W., Sui J., Huang I. C., Kuhn J. H., Radoshitzky S. R., Marasco W. A., Choe H., Farzan M. 2007; The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology 367:367–374 [View Article][PubMed]
    [Google Scholar]
  17. Macnaughton M. R., Hasony H. J., Madge M. H., Reed S. E. 1981; Antibody to virus components in volunteers experimentally infected with human coronavirus 229E group viruses. Infect Immun 31:845–849[PubMed]
    [Google Scholar]
  18. Marra M. A., Jones S. J., Astell C. R., Holt R. A., Brooks-Wilson A., Butterfield Y. S., Khattra J., Asano J. K., Barber S. A. other authors 2003; The genome sequence of the SARS-associated coronavirus. Science 300:1399–1404 [View Article][PubMed]
    [Google Scholar]
  19. Marschall M., Meier-Ewert H., Herrler G., Zimmer G., Maassab H. F. 1997; The cell receptor level is reduced during persistent infection with influenza C virus. Arch Virol 142:1155–1164 [View Article][PubMed]
    [Google Scholar]
  20. Mathewson A. C., Bishop A., Yao Y., Kemp F., Ren J., Chen H., Xu X., Berkhout B., van der Hoek L., Jones I. M. 2008; Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2. J Gen Virol 89:2741–2745 [View Article][PubMed]
    [Google Scholar]
  21. Naniche D., Wild T. F., Rabourdin-Combe C., Gerlier D. 1993; Measles virus haemagglutinin induces down-regulation of gp57/67, a molecule involved in virus binding. J Gen Virol 74:1073–1079 [View Article][PubMed]
    [Google Scholar]
  22. Perlman S., Dandekar A. A. 2005; Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol 5:917–927 [View Article][PubMed]
    [Google Scholar]
  23. Perlman S., Netland J. 2009; Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 7:439–450 [View Article][PubMed]
    [Google Scholar]
  24. Reed S. E. 1984; The behaviour of recent isolates of human respiratory coronavirus in vitro and in volunteers: evidence of heterogeneity among 229E-related strains. J Med Virol 13:179–192 [View Article][PubMed]
    [Google Scholar]
  25. Rota P. A., Oberste M. S., Monroe S. S., Nix W. A., Campagnoli R., Icenogle J. P., Peñaranda S., Bankamp B., Maher K. other authors 2003; Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:1394–1399 [View Article][PubMed]
    [Google Scholar]
  26. Ruijter J. M., Thygesen H. H., Schoneveld O. J., Das A. T., Berkhout B., Lamers W. H. 2006; Factor correction as a tool to eliminate between-session variation in replicate experiments: application to molecular biology and retrovirology. Retrovirology 3:2 [View Article][PubMed]
    [Google Scholar]
  27. Sastre P., Dijkman R., Camuñas A., Ruiz T., Jebbink M. F., van der Hoek L., Vela C., Rueda P. 2011; Differentiation between human coronaviruses NL63 and 229E using a novel double-antibody sandwich enzyme-linked immunosorbent assay based on specific monoclonal antibodies. Clin Vaccine Immunol 18:113–118 [View Article][PubMed]
    [Google Scholar]
  28. Schildgen O., Jebbink M. F., de Vries M., Pyrc K., Dijkman R., Simon A., Müller A., Kupfer B., van der Hoek L. 2006; Identification of cell lines permissive for human coronavirus NL63. J Virol Methods 138:207–210 [View Article][PubMed]
    [Google Scholar]
  29. Smith M. K., Tusell S., Travanty E. A., Berkhout B., van der Hoek L., Holmes K. V. 2006; Human angiotensin-converting enzyme 2 (ACE2) is a receptor for human respiratory coronavirus NL63. Adv Exp Med Biol 581:285–288 [View Article][PubMed]
    [Google Scholar]
  30. Tanner J., Weis J., Fearon D., Whang Y., Kieff E. 1987; Epstein–Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell 50:203–213 [View Article][PubMed]
    [Google Scholar]
  31. Tipnis S. R., Hooper N. M., Hyde R., Karran E., Christie G., Turner A. J. 2000; A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238–33243 [View Article][PubMed]
    [Google Scholar]
  32. van der Hoek L. 2007; Human coronaviruses: what do they cause?. Antivir Ther 12:4 Pt B651–658[PubMed]
    [Google Scholar]
  33. van der Hoek L., Pyrc K., Jebbink M. F., Vermeulen-Oost W., Berkhout R. J., Wolthers K. C., Wertheim-van Dillen P. M., Kaandorp J., Spaargaren J., Berkhout B. 2004; Identification of a new human coronavirus. Nat Med 10:368–373 [View Article][PubMed]
    [Google Scholar]
  34. van der Hoek L., Sure K., Ihorst G., Stang A., Pyrc K., Jebbink M. F., Petersen G., Forster J., Berkhout B., Uberla K. 2005; Croup is associated with the novel coronavirus NL63. PLoS Med 2:e240 [View Article][PubMed]
    [Google Scholar]
  35. van der Hoek L., Ihorst G., Sure K., Vabret A., Dijkman R., de Vries M., Forster J., Berkhout B., Uberla K. 2010; Burden of disease due to human coronavirus NL63 infections and periodicity of infection. J Clin Virol 48:104–108 [View Article][PubMed]
    [Google Scholar]
  36. Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., Godbout K., Parsons T., Baronas E. other authors 2002; Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 277:14838–14843 [View Article][PubMed]
    [Google Scholar]
  37. Warner F. J., Lew R. A., Smith A. I., Lambert D. W., Hooper N. M., Turner A. J. 2005; Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cells. J Biol Chem 280:39353–39362 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.043919-0
Loading
/content/journal/jgv/10.1099/vir.0.043919-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed