1887

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.

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2012-09-01
2019-10-21
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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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [PubMed]
    [Google Scholar]
  22. Perlman S. , Dandekar A. A. . ( 2005; ). Immunopathogenesis of coronavirus infections: implications for SARS. . Nat Rev Immunol 5:, 917–927. [CrossRef] [PubMed]
    [Google Scholar]
  23. Perlman S. , Netland J. . ( 2009; ). Coronaviruses post-SARS: update on replication and pathogenesis. . Nat Rev Microbiol 7:, 439–450. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [PubMed]
    [Google Scholar]
  32. van der Hoek L. . ( 2007; ). Human coronaviruses: what do they cause?. Antivir Ther 12: (4 Pt B), 651–658.[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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [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. [CrossRef] [PubMed]
    [Google Scholar]
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