Skip to main content
PMC home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2004 Feb 23;177(2):559–569. doi: 10.1016/0042-6822(90)90521-R

Mechanisms of transmissible gastroenteritis coronavirus neutralization

Carlos Suñé 1, Gustavo Jiménez 1, Isabel Correa 1, María J Bullido 1, Fatima Gebauer 1, Cristian Smerdou 1, Luis Enjuanes 1,1
PMCID: PMC7131644  PMID: 2164725

Abstract

Transmissible gastroenteritis virus (TGEV) was neutralized more than 109-fold with antibodies of a single specificity [monoclonal antibodies (MAbs)]. Most of the virus was neutralized in the first 2–3 min of a reversible reaction, which was followed by a second phase with a decreased neutralization rate and, in some cases, by a persistent fraction, which was a function of the MAb and of the antibody-to-virus ratio. Neutralization of TGEV is a specific event that requires the location of the epitope involved in the neutralization in the appropriate structural context, which is present in the wild-type virus but not in certain MAb escaping mutants. In neutralization of TGEV by binary combinations of MAbs specific for the same or for different antigenic sites, either no cooperation or a synergistic effect, respectively, was observed. Mechanisms of TGEV neutralization by MAbs were characterized at high, intermediate, and low antibody-to-virus ratios. Under these conditions, mainly three steps of the replication cycle were inhibited: binding of virus to the cell, internalization, and a step that takes place after internalization. In addition, virus aggregation could be responsible for the neutralization of 10 to 20% of virus infectivity.

References

  1. Blondel B., Crainic R., Fichot O., Dufraisse G., Candrea A., Diamond D., Girard M., Horaud F. Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site. J. Virol. 1986;57:81–90. doi: 10.1128/jvi.57.1.81-90.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bullido M.J., Correa I., Jiménez G., Suñé C., Gebauer F., Enjuanes L. Induction of transmissible gastroenteritis coronavirus neutralizing antibodies “in vitro” by virus-specific T helper cell hybridomas. J. Gen. Virol. 1988;70:659–672. doi: 10.1099/0022-1317-70-3-659. [DOI] [PubMed] [Google Scholar]
  3. Cavanagh D., Davis P.J. Coronavirus IBV: Removal of spike glycopolypeptide S1 by urea abolishes infectivity and haemagglutination but not attachment to cells. J. Gen. Virol. 1986;67:1443–1448. doi: 10.1099/0022-1317-67-7-1443. [DOI] [PubMed] [Google Scholar]
  4. Correa I., Gebauer F., Bullido M.J., Suñé C., Baay M.F.D., Zwaagstra K.A., Posthumus W.P.A., Lenstra J.A., Enjuanes L. Localization of antigenic sites of the E2 glycoprotein of transmissible gastroenteritis coronavirus. J. Gen. Virol. 1990;71:271–279. doi: 10.1099/0022-1317-71-2-271. [DOI] [PubMed] [Google Scholar]
  5. Correa I., Jiménez G., Suñé C., Bullido M.J., Enjuanes L. Antigenic structure of the E2 glycoprotein from transmissible gastroenteritis coronavirus. Virus Res. 1988;10:77–94. doi: 10.1016/0168-1702(88)90059-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delmas B., Gelfi J., Laude H. Antigenic structure of transmissible gastroenteritis virus. II. Domains in the peplomer glycoprotein. J. Gen. Virol. 1986;65:1405–1418. doi: 10.1099/0022-1317-67-7-1405. [DOI] [PubMed] [Google Scholar]
  7. Dimmock N.J. Mechanisms of neutralization of animal viruses. J. Gen. Virol. 1984;65:1015–1022. doi: 10.1099/0022-1317-65-6-1015. [DOI] [PubMed] [Google Scholar]
  8. Dimmock N.J. Multiple mechanisms of neutralization of animal viruses. Trends Biochem. Sci. 1987;13:70–75. [Google Scholar]
  9. Enjuanes L., Gebauer F., Correa I., Bullido M.J., Suñé C., Smerdou C., Sánchez C., Lenstra J.A., Posthumus W.P.A., Meloen R. Location of antigenic sites of the S-glycoprotein of transmissible gastroenteritis virus and their conservation in coronaviruses. Adv. Exp. Biol. Med. 1990 doi: 10.1007/978-1-4684-5823-7_23. in press. [DOI] [PubMed] [Google Scholar]
  10. Fleming J.C., Trousdale M.D., El-Zaatari F.A.K., Stholman S.D., Weiner L.P. Pathogenicity of antigenic variants of murine coronavirus 1HM selected with monoclonal antibodies. J. Virol. 1986;58:869–875. doi: 10.1128/jvi.58.3.869-875.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fuller A.O., Santos R.E., Spear P.G. Neutralizing antibodies specific for glycoprotein H of herpes simplex virus permit viral attachment to cells but prevent penetration. J. Virol. 1989;63:3435–3443. doi: 10.1128/jvi.63.8.3435-3443.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fuller A.O., Spear P.G. Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralizing antibodies. J. Virol. 1985;55:475–482. doi: 10.1128/jvi.55.2.475-482.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garwes D.J., Lucas M.H., Higgins D.A., Pike B.V., Cartwright S.F. Antigenicity of structural components from porcine transmissible gastroenteritis virus. Vet. Microbiol. 1978;3:179–190. [Google Scholar]
  14. Garwes D.J., Pocock D.H., Picke B.V. Isolation of subviral components from transmissible gastroenteritis virus. J. Gen. Virol. 1976;32:283–294. doi: 10.1099/0022-1317-32-2-283. [DOI] [PubMed] [Google Scholar]
  15. Highlander S.L., Sutherland S.L., Gage P.J., Johnson D.C., Levine M., Glorioso J.C. Neutralizing monoclonal antibodies specific for herpes simplex virus glycoprotein inhibit virus penetration. J. Virol. 1987;61:3356–3364. doi: 10.1128/jvi.61.11.3356-3364.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Holmes K.V., Williams R.K., Stephensen C.B., Compton S.R., Cardellichio C.B., Hay C.M., Knobler R.L., Weismiller D.G., Boyle J.F. In: Cell Biology of Virus Entry, Replication, and Pathogenesis. Compans R.W., Helenius A., Oldstone M.B.A., editors. Alan R. Liss; New York: 1989. Coronavirus receptors; pp. 85–95. [Google Scholar]
  17. Huang A.S., Wagner R.R. Vol. 116. 1964. Penetration of herpes simplex virus into human epidermoid cells; pp. 863–869. (Proc. Soc. Exp. Biol. Med.). [DOI] [PubMed] [Google Scholar]
  18. Icenogle J., Shiwen H., Duke G., Gilbert S., Rueckert R., Anderegg J. Neutralization of poliovirus by a monoclonal antibody: Kinetics and stoichiometry. Virology. 1983;127:412–425. doi: 10.1016/0042-6822(83)90154-x. [DOI] [PubMed] [Google Scholar]
  19. Jiménez G., Correa I., Melgosa M.P., Bullido M.J., Enjuanes L. Critical epitopes in transmissible gastroenteritis virus neutralization. J. Virol. 1986;60:131–139. doi: 10.1128/jvi.60.1.131-139.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kapke P.A., Brian D.A. Sequence analysis of the porcine transmissible gastroenteritis coronavirus nucleocapsid protein gene. Virology. 1986;151:41–49. doi: 10.1016/0042-6822(86)90102-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laude H., Chapsal J.M., Gelfi J., Labian S., Grosclaude J. Antigenic structure of transmissible gastroenteritis virus. I. Properties of monoclonal antibodies directed against virion proteins. J. Gen. Virol. 1986;67:119–130. doi: 10.1099/0022-1317-67-1-119. [DOI] [PubMed] [Google Scholar]
  22. Laude H., Raschaert D., Huet J.C. Sequence and N-terminal processing of the transmembrane protein E1 of the coronavirus transmissible gastroenteritis virus. J. Gen. Virol. 1987;68:1687–1693. doi: 10.1099/0022-1317-68-6-1687. [DOI] [PubMed] [Google Scholar]
  23. Mandel B. In: Fraenkel-Conrat H., Wagner R.R., editors. Plenum; New York: 1979. Interactions of viruses with neutralizing antibodies; p. 37. (Comprehensive Virology, Vol. 15, Virus-Host Interactions. Immunity to Viruses). [Google Scholar]
  24. McClurkin A.W., Norman J.O. Studies on transmissible gastroenteritis of swine. II. Selected characteristics of a cytopathogenic virus common to five isolates from transmissible gastroenteritis. Canad. J. Comp. Med. Vet. Sci. 1966;30:190–198. [PMC free article] [PubMed] [Google Scholar]
  25. Miller N., Hutt-Fletcher L.M. A monoclonal antibody to glycoproteln gp85 inhibits fusion but not attachment of Epstein-Barr virus. J. Virol. 1988;62:2366–2372. doi: 10.1128/jvi.62.7.2366-2372.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mockett A.P.A., Cavanagh D., Brown T.D.K. Monoclonal antibodies to the S1 spike and membrane proteins of avian infectious bronchitis coronavirus strain Massachusetts M41. J. Gen. Virol. 1984;65:2281–2286. doi: 10.1099/0022-1317-65-12-2281. [DOI] [PubMed] [Google Scholar]
  27. Nguyen T.D., Bottreau E., Bernard S., Lantier I., Aynaud J.M. Neutralizing secretory IgA and IgG do not inhibit attachment of transmissible gastroenteritis virus. J. Gen. Virol. 1986;67:57–61. doi: 10.1099/0022-1317-67-5-939. [DOI] [PubMed] [Google Scholar]
  28. Posthumus W.P.A., Meloen R.H., Enjuanes L., Correa I., Van Nieuwstadt A.P.K., Koch G., De Groot R.J., Kusters J.G., Luytjes W., Spaan W.J., Van Der Zeijst B.A.M., Lenstra J.A. Linear neutralizing epitopes on the peplomer protein of coronaviruses. Adv. Exp. Med. Biol. 1990 doi: 10.1007/978-1-4684-5823-7_25. in press. [DOI] [PubMed] [Google Scholar]
  29. Rasschaert D., Laude H. The predicted primary structure of the peplomer protein E2 of porcine coronavirus transmissible gastroenteritis virus. J. Gen. Virol. 1987;68:1883–1890. doi: 10.1099/0022-1317-68-7-1883. [DOI] [PubMed] [Google Scholar]
  30. Rigg R.J., Carver A.S., Dimmock N.J. IgG-neutralizing influenza virus undergoes primary, but not secondary uncoating in vivo. J. Gen. Virol. 1989;70:2097–2109. doi: 10.1099/0022-1317-70-8-2097. [DOI] [PubMed] [Google Scholar]
  31. Sachs D., Leight G., Cone J., Schwarz S., Stuart L.Z., Rosemberg S. Transplantation in miniature swine. I. Fixation of the major histocompatibility complex. Transplantation. 1976;22:559–567. doi: 10.1097/00007890-197612000-00004. [DOI] [PubMed] [Google Scholar]
  32. Saif L.J., Bohl E.H. In: Diseases of Swine. 6th ed. Leman A.D., Straw B., Glock R.D., Mengeling W.L., Penny R.H.C., Scholl E., editors. Iowa State Univ. Press; Ames: 1986. Transmissible gastroenteritis; pp. 255–274. [Google Scholar]
  33. Sánchez C.M., Jiménez G., Laviada M.D., Correa I., Suñe C., Bullido M.J., Gebauer F., Smerdou C., Callebaut P., Escribano J.A.M., Enjuanes L. Antigenic homology among coronaviruses related to transmissible gastroenteritis virus. Virology. 1990;174:410–417. doi: 10.1016/0042-6822(90)90094-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sanz A., Garcia-Barreno B., Nogal M.L., Viñuela E., Enjuanes L. Monoclonal antibodies specific for African swine fever virus proteins. J. Virol. 1985;54:199–206. doi: 10.1128/jvi.54.1.199-206.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Siddell S., Wege H., Ter Mellen V. The biology of coronaviruses. J. Gen. Virol. 1983;64:761–776. doi: 10.1099/0022-1317-64-4-761. [DOI] [PubMed] [Google Scholar]
  36. Sturman L.S., Holmes K.V. The molecular biology of coronaviruses. Adv. Viral Res. 1983;28:35–112. doi: 10.1016/S0065-3527(08)60721-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Talbot P.J., Salmi A.A., Knobler R.L., Buchmeier M.J. Topographical mapping of epitopes on the glycoproteins of murine hepatitis virus-4 (Strain JHM): Correlation with biological activities. Virology. 1984;132:250–260. doi: 10.1016/0042-6822(84)90032-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wege H., Dörries R., Wege H. Hybridoma antibodies to the murine coronavirus JHM: Characterization of epitopes on the peplomer protein (E2) J. Gen. Virol. 1984;65:1931–1942. doi: 10.1099/0022-1317-65-11-1931. [DOI] [PubMed] [Google Scholar]
  39. Wohlfart C.E.G. Neutralization of adenoviruses: Kinetics, stoichiometry, and mechanisms. J. Virol. 1988;62:2321–2328. doi: 10.1128/jvi.62.7.2321-2328.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wohlfart C.E.G., Svensson U.K., Everitt E. Interaction between HeLa cells and adenovirus type 2 virions neutralized by different antisera. J. Virol. 1985;56:896–903. doi: 10.1128/jvi.56.3.896-903.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Woods R.D., Wesley R.D., Kapke P.A. Complement-dependent neutralization of transmissible gastroenteritis virus by monoclonal antibodies. Adv. Exp. Med. Biol. 1987;218:493–500. doi: 10.1007/978-1-4684-1280-2_64. [DOI] [PubMed] [Google Scholar]

Articles from Virology are provided here courtesy of Elsevier

RESOURCES