1887

Abstract

Coronaviruses are enveloped RNA viruses that have evolved complex relationships with their host cells, and modulate their lipid composition, lipid synthesis and signalling. Lipid rafts, enriched in sphingolipids, cholesterol and associated proteins, are special plasma membrane microdomains involved in several processes in viral infections. The extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to lipid rafts. Because cholesterol-rich microdomains appear to be a general feature of the entry mechanism of non-eneveloped viruses and of several coronaviruses, the purpose of this study was to analyse the contribution of lipids to the infectivity of canine coronavirus (CCoV). The CCoV life cycle is closely connected to plasma membrane cholesterol, from cell entry to viral particle production. The methyl-β-cyclodextrin (MβCD) was employed to remove cholesterol and to disrupt the lipid rafts. Cholesterol depletion from the cell membrane resulted in a dose-dependent reduction, but not abolishment, of virus infectivity, and at a concentration of 15 mM, the reduction in the infection rate was about 68 %. MβCD treatment was used to verify if cholesterol in the envelope was required for CCoV infection. This resulted in a dose-dependent inhibitory effect, and at a concentration of 9 mM MβCD, infectivity was reduced by about 73 %. Since viral entry would constitute a target for antiviral strategies, inhibitory molecules interacting with viral and/or cell membranes, or interfering with lipid metabolism, may have strong antiviral potential. It will be interesting in the future to analyse the membrane microdomains in the CCoV envelope.

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2015-02-01
2024-03-28
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References

  1. Ahn A., Gibbons D. L., Kielian M. 2002; The fusion peptide of Semliki Forest virus associates with sterol-rich membrane domains. J Virol 76:3267–3275 [View Article][PubMed]
    [Google Scholar]
  2. Anderson H. A., Chen Y., Norkin L. C. 1996; Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae. Mol Biol Cell 7:1825–1834 [View Article][PubMed]
    [Google Scholar]
  3. Barman S., Nayak D. P. 2007; Lipid raft disruption by cholesterol depletion enhances influenza A virus budding from MDCK cells. J Virol 81:12169–12178 [View Article][PubMed]
    [Google Scholar]
  4. Bavari S., Bosio C. M., Wiegand E., Ruthel G., Will A. B., Geisbert T. W., Hevey M., Schmaljohn C., Schmaljohn A., Aman M. J. 2002; Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. J Exp Med 195:593–602 [View Article][PubMed]
    [Google Scholar]
  5. Bender F. C., Whitbeck J. C., Ponce de Leon M., Lou H., Eisenberg R. J., Cohen G. H. 2003; Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry. J Virol 77:9542–9552 [View Article][PubMed]
    [Google Scholar]
  6. Binn L. N., Marchwicki R. H., Stephenson E. H. 1980; Establishment of a canine cell line: derivation, characterization, and viral spectrum. Am J Vet Res 41:855–860[PubMed]
    [Google Scholar]
  7. Blaising J., Pécheur E.-I. 2013; Lipids: a key for hepatitis C virus entry and a potential target for antiviral strategies. Biochimie 95:96–102 [View Article][PubMed]
    [Google Scholar]
  8. Choi K. S., Aizaki H., Lai M. M. 2005; Murine coronavirus requires lipid rafts for virus entry and cell-cell fusion but not for virus release. J Virol 79:9862–9871 [View Article][PubMed]
    [Google Scholar]
  9. Desplanques A. S., Nauwynck H. J., Vercauteren D., Geens T., Favoreel H. W. 2008; Plasma membrane cholesterol is required for efficient pseudorabies virus entry. Virology 376:339–345 [View Article][PubMed]
    [Google Scholar]
  10. Funk A., Mhamdi M., Hohenberg H., Heeren J., Reimer R., Lambert C., Prange R., Sirma H. 2008; Duck hepatitis B virus requires cholesterol for endosomal escape during virus entry. J Virol 82:10532–10542 [View Article][PubMed]
    [Google Scholar]
  11. Glende J., Schwegmann-Wessels C., Al-Falah M., Pfefferle S., Qu X., Deng H., Drosten C., Naim H. Y., Herrler G. 2008; Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2. Virology 381:215–221 [View Article][PubMed]
    [Google Scholar]
  12. Guyader M., Kiyokawa E., Abrami L., Turelli P., Trono D. 2002; Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization. J Virol 76:10356–10364 [View Article][PubMed]
    [Google Scholar]
  13. Hambleton S., Steinberg S. P., Gershon M. D., Gershon A. A. 2007; Cholesterol dependence of varicella-zoster virion entry into target cells. J Virol 81:7548–7558 [View Article][PubMed]
    [Google Scholar]
  14. Imhoff H., von Messling V., Herrler G., Haas L. 2007; Canine distemper virus infection requires cholesterol in the viral envelope. J Virol 81:4158–4165 [View Article][PubMed]
    [Google Scholar]
  15. Lai M. M. C., Holmes K. V. 2001; Coronaviridae: the viruses and their replication. In Fields Virology pp. 1163–1185 Edited by Knipe D. M., Howley P. M., Griffin D. E., Lamb R. A., Martin M. A., Roizman B., Strais S. E. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  16. Li G. M., Li Y. G., Yamate M., Li S. M., Ikuta K. 2007; Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle. Microbes Infect 9:96–102 [View Article][PubMed]
    [Google Scholar]
  17. Liao Z., Cimakasky L. M., Hampton R., Nguyen D. H., Hildreth J. E. 2001; Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. AIDS Res Hum Retroviruses 17:1009–1019 [View Article][PubMed]
    [Google Scholar]
  18. Liao Z., Graham D. R., Hildreth J. E. 2003; Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. AIDS Res Hum Retroviruses 19:675–687 [View Article][PubMed]
    [Google Scholar]
  19. Lu X., Xiong Y., Silver J. 2002; Asymmetric requirement for cholesterol in receptor-bearing but not envelope-bearing membranes for fusion mediated by ecotropic murine leukemia virus. J Virol 76:6701–6709 [View Article][PubMed]
    [Google Scholar]
  20. Nomura R., Kiyota A., Suzaki E., Kataoka K., Ohe Y., Miyamoto K., Senda T., Fujimoto T. 2004; Human coronavirus 229E binds to CD13 in rafts and enters the cell through caveolae. J Virol 78:8701–8708 [View Article][PubMed]
    [Google Scholar]
  21. Phalen T., Kielian M. 1991; Cholesterol is required for infection by Semliki Forest virus. J Cell Biol 112:615–623 [View Article][PubMed]
    [Google Scholar]
  22. Pratelli A. 2006; Genetic evolution of canine coronavirus and recent advances in prophylaxis. Vet Res 37:191–200 [View Article][PubMed]
    [Google Scholar]
  23. Pratelli A. 2011; The evolutionary processes of canine coronaviruses. Adv Virol 2011:562831 [View Article][PubMed]
    [Google Scholar]
  24. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497
    [Google Scholar]
  25. Ren X., Glende J., Yin J., Schwegmann-Wessels C., Herrler G. 2008; Importance of cholesterol for infection of cells by transmissible gastroenteritis virus. Virus Res 137:220–224 [View Article][PubMed]
    [Google Scholar]
  26. Sevlever D., Pickett S., Mann K. J., Sambamurti K., Medof M. E., Rosenberry T. L. 1999; Glycosylphosphatidylinositol-anchor intermediates associate with triton-insoluble membranes in subcellular compartments that include the endoplasmic reticulum. Biochem J 343:627–635 [View Article][PubMed]
    [Google Scholar]
  27. Sun X., Whittaker G. R. 2003; Role for influenza virus envelope cholesterol in virus entry and infection. J Virol 77:12543–12551 [View Article][PubMed]
    [Google Scholar]
  28. Suzuki T., Suzuki Y. 2006; Virus infection and lipid rafts. Biol Pharm Bull 29:1538–1541 [View Article][PubMed]
    [Google Scholar]
  29. Thorp E. B., Gallagher T. M. 2004; Requirements for CEACAMs and cholesterol during murine coronavirus cell entry. J Virol 78:2682–2692 [View Article][PubMed]
    [Google Scholar]
  30. Tooze J., Tooze S., Warren G. 1984; Replication of coronavirus MHV-A59 in sac-cells: determination of the first site of budding of progeny virions. Eur J Cell Biol 33:281–293[PubMed]
    [Google Scholar]
  31. Umashankar M., Sánchez-San Martín C., Liao M., Reilly B., Guo A., Taylor G., Kielian M. 2008; Differential cholesterol binding by class II fusion proteins determines membrane fusion properties. J Virol 82:9245–9253 [View Article][PubMed]
    [Google Scholar]
  32. 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]
  33. Yin J., Glende J., Schwegmann-Wessels C., Enjuanes L., Herrler G., Ren X. 2010; Cholesterol is important for a post-adsorption step in the entry process of transmissible gastroenteritis virus. Antiviral Res 88:311–316 [View Article][PubMed]
    [Google Scholar]
  34. Zhu L., Ding X., Tao J., Wang J., Zhao X., Zhu G. 2010; Critical role of cholesterol in bovine herpesvirus type 1 infection of MDBK cells. Vet Microbiol 144:51–57 [View Article][PubMed]
    [Google Scholar]
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