Abstract
The antigenic structure of the S glycoprotein of transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) has been determined and correlated with the physical structure. Four antigenic sites have been defined (A, B, C, and D). The sites involved in the neutralization of TGEV are: A, D, and B, sites A and D being antigenically dominant for TGEV neutralization in vitro. These two sites have specific properties of interest: site A is highly conserved and is present in coronaviruses of three animal species, and site D can be represented by synthetic peptides. Both sites might be relevant in protection in vivo. PRCV does not have sites B and C, due to a genomic deletion. Complex antigenic sites, i.e., conformation and glycosylation dependent sites, have been represented by simple mimotopes selected from a library expressing recombinant peptides with random sequences, or by anti-idiotypic internal image monoclonal antibodies. An epidemiological tree relating the TGEVs and PRCVs has been proposed. The estimated mutation fixation rate of 7 ± 2 × 10−4 substitutions per nucleotide and year indicates that TGEV related coronaviruses show similar variability to other RNA viruses. In order to induce secretory immunity, different segments of the S gene have been expressed using avirulent forms of Salmonella typhimurium and adenovirus. These vectors, with a tropism for Peyer's patches may be ideal candidates in protection against TGEV.
References
- Ausubel F.M., Brent R., Kingston R.E., Moore D.D., Seidman J.G., Smith J.A., Struhl K. Wiley Inc; New York: 1991. Current protocols in molecular biology. [Google Scholar]
- Britton P., Page K.W. Sequence of the S-Gene from a virulent british field isolate of transmissible gastroenteritis virus. Virus Res. 1990;18:71–80. doi: 10.1016/0168-1702(90)90090-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Callebaut P., Correa I., Pensaert M., Jiménez G., Enjuanes L. Antigenic differentiation between transmissible gastroenteritis virus of swine and a related porcine respiratory coronavirus. J. Gen. Virol. 1988;69:1725–1730. doi: 10.1099/0022-1317-69-7-1725. [DOI] [PubMed] [Google Scholar]
- 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]
- Correa I., Jiménez G., Suñé C., Bullido M.J., Enjuanes L. Antigenic structure of the E2 glycoprotein from transmissible gastroenteritis coronavirus. Vir. Res. 1988;10:77–94. doi: 10.1016/0168-1702(88)90059-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cos E., Hooyberghs J., Pensaert M.B. Sites of replication of a porcine respiratory coronavirus related to transmissible gastroenteritis virus. Res. Vet. Sci. 1990;48:165–169. doi: 10.1016/S0034-5288(18)30984-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cos E., Pensaert M.B., Callebaut P., van Deun K. Intestinal replication of a porcine respiratory coronavirus closely related antigenically to the enteric transmissible gastroenteritis virus. Vet. Microbiol. 1990;23:237–243. doi: 10.1016/0378-1135(90)90154-N. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curtiss R., III, Galan J.E., Nakayama K., Kelly S.M. Stabilization of recombinant avirulent strains in vivo. Res. Microbiol. 1990;141:797–805. doi: 10.1016/0923-2508(90)90113-5. [DOI] [PubMed] [Google Scholar]
- Curtiss R., III, Kelly M.S. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect. Immun. 1987;55:3035–3043. doi: 10.1128/iai.55.12.3035-3043.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Groot R.J., Luytjes W., Horzinek M.C., Van der Zeijst B.A.M., Spaan W.J.M., Lenstra J.A. Evidence for a coiled-coil structure in the spike protein of coronaviruses. J. Mol. Biol. 1987;196:963–966. doi: 10.1016/0022-2836(87)90422-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delmas B., Gelfi J., Laude H. Antigenic structure of transmissible gastroenteritis virus. II. Domains in the peplomer glycoprotein. J. Gen. Virol. 1986;67:1405–1418. doi: 10.1099/0022-1317-67-7-1405. [DOI] [PubMed] [Google Scholar]
- Delmas B., Rasschaert D., Godet M., Gelfi J., Laude H. Four major antigenic sites of the coronavirus transmissible gastroenteritis virus are located on the amino-terminal half of spike protein. J. Gen. Virol. 1990;71:1313–1323. doi: 10.1099/0022-1317-71-6-1313. [DOI] [PubMed] [Google Scholar]
- Domingo E., Holland J.J. High error rates, population equilibrium and evolution of RNA replication systems. In: Domingo E., Holland J.J., Ahlquist P., editors. RNA genetics. CRC Press; Boca Ratón, Florida: 1988. pp. 3–36. [Google Scholar]
- Doyle L.P., Hutchings L.M. A transmissible gastroenteritis in pigs. J. Am. Vet. Med. Assoc. 1946;108:257–259. [PubMed] [Google Scholar]
- Felsenstein J. University Herbarium University of California; Berkeley, California: 1990. PHYLIP manual version version 3.3. [Google Scholar]
- Fichot O., Girard M. An improved method for sequencing of RNA templates. Nucleic Acids Res. 1990;18:6162. doi: 10.1093/nar/18.20.6162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garwes D.J., Stewart F., Cartwright S.F., Brown I. Differentiation of porcine coronavirus from transmissible gastroenteritis virus. Vet. Rec. 1988;122:86–87. doi: 10.1136/vr.122.4.86. [DOI] [PubMed] [Google Scholar]
- Gebauer F., Posthumus W.A.P., Correa I., Suñé C., Sánchez C.M., Smerdou C., Lenstra J.A., Meloen R., Enjuanes L. Residues involved in the formation of the antigenic sites of the S protein of transmissible gastroenteritis coronavirus. Virology. 1991;183:225–238. doi: 10.1016/0042-6822(91)90135-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geysen N.M., Meloen R.H., Barteling S.J. Vol. 81. 1984. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid; pp. 3998–4002. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham F.L., Prevec L. Manipulation of Adenovirus vectors. In: Murray E.J., Walker J.M., editors. Humana Press; Clifton, New Jersey: 1991. pp. 109–128. (Methods in Molecular Biology, vol. 7. Gene transfer and expression techniques). [DOI] [PubMed] [Google Scholar]
- 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]
- Jukes T.H., Cantor C.R. Evolution of protein molecules. In: Munro H.N., editor. Mammalian protein metabolism. Academic Press; New York: 1969. pp. 21–132. [Google Scholar]
- Kimura M. Cambridge University Press; Cambridge: 1983. The neutral theory of molecular evolution. [Google Scholar]
- Lenstra J.A., Erkens J.H.F., Zwaagstra K.A., Posthumus W.P.A., Meloen P.H., Gebauer F., Enjuanes L., Stanley K.K. Selection of mimotopes from a random sequence expression library by monoclonal antibodies against transmissible gastroenteritis coronavirus. J. Immunol. Methods. 1992;52:149–157. doi: 10.1016/0022-1759(92)90136-H. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moxley R.A., Olson L.D., Solorzano R.F. Relationship among transmissible gastroenteritis virus antibody titers in serum, colostrum, and milk from vaccinated sows, and protection in their suckling pigs. Am. J. Vet. Res. 1989;50:119–125. [PubMed] [Google Scholar]
- Nakayama K., Kelly S.M., Curtiss R., III Construction of an asd+ expression-cloning vector: stable maintenance and high level expression of cloned genes in a Salmonella vaccine strain. Biotechnology. 1988;6:693–697. [Google Scholar]
- Pensaert M., Callebaut P., Vergote J. Isolation of a porcine respiratory, non-enteric coronavirus related to transmissible gastroenteritis. Vet. Q. 1986;8:257–260. doi: 10.1080/01652176.1986.9694050. [DOI] [PubMed] [Google Scholar]
- Posthumus W.P.A., Lenstra J.A., Schaaper W.M.M., van Nieuwstadt A.P., Enjuanes L., Meloen R.H. Analysis and simulation of a neutralizing epitope of transmissible gastroenteritis virus. J. Virol. 1990;64:3304–3309. doi: 10.1128/jvi.64.7.3304-3309.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rasschaert D., Duarte M., Laude H. Porcine respiratory coronavirus differs from transmissible gastroenteritis virus by a few genomic deletions. J. Gen. Virol. 1990;71:2599–2607. doi: 10.1099/0022-1317-71-11-2599. [DOI] [PubMed] [Google Scholar]
- Saituo N.M., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 1987;4:406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
- Sambrook J., Fritsch E.F., Maniatis T. Cold Spring Harbor Laboratory; Cold Spring Harbor, New York: 1989. Molecular cloning: a laboratory manual. [Google Scholar]
- Sánchez C.M., Gebauer F., Suñé C., Dopazo J., Enjuanes L. Genetic evolution of transmissible gastroenteritis coronaviruses. Virology. 1992;Vol. 190 doi: 10.1016/0042-6822(92)91195-Z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sánchez C.M., Jiménez G., Laviada M.D., Gorrea I., Suñé C., Bullido M.J., Gebauer F., Smerdou C., Callebaut P., Escribano J.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]
- Sanger F., Nicklen S., Coulson A.R. Vol. 74. 1977. DNA sequencing with chain-terminating inhibitors; pp. 5463–5467. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sourdis J., Nei M. Relative efficiencies of the maximum parsimony and distance-matrix methods in obtaining the correct phylogenetic tree. Mol. Biol. Evol. 1988;45:298–311. doi: 10.1093/oxfordjournals.molbev.a040497. [DOI] [PubMed] [Google Scholar]
- Spaan W., Cavanagh D., Horzinek M.C. Coronaviruses: structure and genome expression. J. Gen. Virol. 1988;69:2939–2952. doi: 10.1099/0022-1317-69-12-2939. [DOI] [PubMed] [Google Scholar]
- Suñé C., Jiménez G., Correa I., Bullido M.J., Gebauer F., Smerdou C., Enjuanes L. Mechanisms of transmissible gastroenteritis coronavirus neutralization. Virology. 1990;177:559–569. doi: 10.1016/0042-6822(90)90521-R. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suñé C., Smerdou C., Antón I.M., Abril P., Plana J., Enjuanes L. Anti-idiotypic monoclonal antibodies mimicking an inter species-specific epitope critical in coronavirus neutralization. J. Virol. 1991;65:6969–6978. doi: 10.1128/jvi.65.12.6979-6984.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wesley R.D., Woods R.D., Cheung A.K. Genetic analysis of porcine respiratory coronavirus, an attenuated variant of tranmissible gastroenteritis virus. J. Virol. 1991;65:3369–3373. doi: 10.1128/jvi.65.6.3369-3373.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wesley R.D., Woods R.D., Hill H.T., Biwer J.D. Evidence for a porcine respiratory coronavirus, antigenically similar to transmisiible gastroenteritis virus, in the United States. J. Vet. Diagn. Invest. 1990;2:312–317. doi: 10.1177/104063879000200411. [DOI] [PubMed] [Google Scholar]
