Skip to main content
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2002 Nov 12;22(2):125–141. doi: 10.1016/0168-1702(92)90039-C

Sequence analysis of human coronavirus 229E mRNAs 4 and 5: evidence for polymorphism and homology with myelin basic protein

Patricia Jouvenne 1, Samir Mounir 1, Janet N Stewart 1, Christopher D Richardson 2, Pierre J Talbot 1,
PMCID: PMC7134066  PMID: 1373555

Abstract

Human coronaviruses (HCV) are important pathogens responsible for respiratory, gastrointestinal and possibly neurological disorders. To better understand the molecular biology of the prototype HCV-229E strain, the nucleotide sequence of the 5'-unique regions of mRNAs 4 and 5 were determined from cloned cDNAs. Sequence analysis of the cDNAs synthesized from mRNA 4 revealed a major difference with previously published results. However, polymerase chain reaction amplification of this region showed that the sequenced cDNAs were produced from minor RNA species, an indication of possible genetic polymorphism in this region of the viral genome. The mutated messenger RNA 4 contains two ORFs: (1) ORF4a consisting of 132 nucleotides which potentially encodes a 44-amino acid polypeptide of 4653 Da; this coding sequence is preceded by a consensus transcriptional initiation sequence, CUAAACU, similar to the ones found upstream of the N and M genes; (2) ORF4b of 249 nucleotides potentially encoding an 83-amino acid basic and leucine-rich polypeptide of 9550 Da. On the other hand, mRNA 5 contains one single ORF of 231 nucleotides which could encode a 77-amino acid basic and leucine-rich polypeptide of 9046 Da. This putative protein presents a significant degree of amino acid homology (33%) with its counterpart found in transmissible gastroenteritis coronavirus (TGEV). The proteins in the two different viruses exhibit similar molecular weights and are extremely hydrophobic. Interestingly, a sequence homology of five amino acids was found between the protein encoded by ORF4b of HCV-229E and an immunologically important region of human myelin basic protein.

Keywords: Coronavirus, Human, 229E, Myelin basic protein, Polymorphism, mRNA 4, mRNA 5, Nucleotide sequence

References

  1. Abel T., Maniatis T. Action of leucine zippers. Nature (Lond.) 1989;341:24–25. doi: 10.1038/341024a0. [DOI] [PubMed] [Google Scholar]
  2. Abraham S., Kienzle T.E., Lapps W.E., Brian D.A. Sequence and expression analysis of potential nonstructural proteins of 4.9, 4.8, 12.7, and 9.5 kDa encoded between the spike and membrane protein genes of the bovine coronavirus. Virology. 1990;177:488–495. doi: 10.1016/0042-6822(90)90513-Q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allegretta M., Nicklas J.A., Sriram S., Albertini R.J. T-cells responsive to myelin basic protein in patients with multiple sclerosis. Science. 1990;247:718–721. doi: 10.1126/science.1689076. [DOI] [PubMed] [Google Scholar]
  4. Arpin N., Talbot P.J. Molecular characterization of the 229E strain of human coronavirus. In: Cavanagh D., Brown T.D.K., editors. Coronaviruses and Their Diseases. Vol. 276. Plenum; New York: 1990. pp. 73–80. (Advances in Experimental Medicine and Biology). [DOI] [PubMed] [Google Scholar]
  5. Boursnell M.E.G., Brown T.D.K. Sequencing of coronavirus IBV genomic RNA: a 195-base open reading frame encoded by mRNA B. Gene. 1984;29:87–92. doi: 10.1016/0378-1119(84)90169-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boursnell M.E.G., Binns M.M., Brown T.D.K. Sequencing of coronavirus IBV genomic RNA: three open-reading frames in the 5' ‘unique’ region of mRNA D. J. Gen. Virol. 1985;66:2253–2258. doi: 10.1099/0022-1317-66-10-2253. [DOI] [PubMed] [Google Scholar]
  7. Britton P., Lopez Otin C., Martin Alonson J.M., Parra F. Sequence of the coding regions from the 3.0 kb and 3.9 kb mRNA subgenomic species from a virulent isolate of transmissible gastroenteritis virus. Arch. Virol. 1989;105:165–178. doi: 10.1007/BF01311354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Budzilowicz C.J., Weiss S.R. In vitro synthesis of two polypeptides from a non-structural gene of coronavirus mouse hepatitis virus strain A59. Virology. 1987;157:509–515. doi: 10.1016/0042-6822(87)90293-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Burks J.S., DeVald B.L., Jankovsky L.D., Gerdes J.C. Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients. Science. 1980;209:933–934. doi: 10.1126/science.7403860. [DOI] [PubMed] [Google Scholar]
  10. Carnegie P.R. Amino acid sequence of the encephalitogenic basic protein from human myelin. Biochem. J. 1971;123:57–67. doi: 10.1042/bj1230057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cavanagh D., Brian D.A., Enjuanes L., Holmes K.V., Lai M.M.C., Laude H., Siddell S.G., Spaan W., Taguchi F., Talbot P.J. Recommendations of the Coronavirus Study Group for the nomenclature of the structural proteins, mRNAs, and genes of coronaviruses. Virology. 1990;176:306–307. doi: 10.1016/0042-6822(90)90259-T. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Daniel C., Talbot P.J. Physico-chemical properties of murine hepatitis virus, strain A59. Arch. Virol. 1987;96:241–248. doi: 10.1007/BF01320963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davis E.V., Bolin V.S. Vol. 19. 1960. Continuous cultivation of isogenous cell lines from the human embryo; p. 386. (Fed. Proc.). [Google Scholar]
  14. Devereux J., Haeberii P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucl. Acids Res. 1981;12:387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Evans R.M., Hollenberg S.M. Zinc fingers: gilt by association. Cell. 1988;52:1–3. doi: 10.1016/0092-8674(88)90522-3. [DOI] [PubMed] [Google Scholar]
  16. Favaloro J., Treisman R., Kamen R. Vol. 65. Academic Press; New York: 1980. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclei's S1 gel mapping; pp. 718–749. (Methods in Enzymology). [DOI] [PubMed] [Google Scholar]
  17. Fishman P.S., Gass J.S., Swoveland P.T., Lavi E., Highkin M.K., Weiss S.R. Infection of the basal ganglia by a murine coronavirus. Science. 1985;229:877–879. doi: 10.1126/science.2992088. [DOI] [PubMed] [Google Scholar]
  18. Fritz R.B., McFarlin D.E. Encephalitogenic epitopes of myelin basic protein. In: Sercarz E., editor. Antigenic determinants and immune regulation. Karger; Basel: 1989. pp. 101–125. [PubMed] [Google Scholar]
  19. Fujinami R.S., Oldstone M.B.A. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science. 1985;230:1043–1045. doi: 10.1126/science.2414848. [DOI] [PubMed] [Google Scholar]
  20. Geysen H.M., Mason T.J., Rodda S.J. Cognitive features of continuous antigenic determinants. In: Tam J.P., Kaiser E.T., editors. Synthetic Peptides: Approaches to Biological Problems. Liss; New York: 1989. pp. 19–30. [Google Scholar]
  21. Grunstein M., Hogness D.S. Vol. 72. 1975. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene; pp. 3961–3965. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hashim G., Vandenbark A.A., Gold D.P., Diamanduros T., Offner H. T-cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats. J. Immunol. 1991;146:515–520. [PubMed] [Google Scholar]
  23. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal. Biochem. 1986;152:232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  24. Hierholzer J.C. Purification and biophysical properties of human coronavirus 229E. Virology. 1976;75:155–165. doi: 10.1016/0042-6822(76)90014-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hierholzer J.C., Kemp M.C., Tannock G.A. The RNA and proteins of human coronaviruses. In: ter Meulen V., Siddell S., Wege H., editors. Biochemistry and Biology of Coronaviruses. Vol. 142. Plenum; New York: 1981. pp. 43–69. (Advances in Experimental Medicine and Biology). [DOI] [PubMed] [Google Scholar]
  26. Jahnke U., Fischer E.H., Alvord E.C., Jr. Sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis. Science. 1985;229:282–284. doi: 10.1126/science.2409602. [DOI] [PubMed] [Google Scholar]
  27. Jingwu Z., Chou C.H.J., Hashim G., Medear R., Raus J.C.M. Preferential peptide specificity and HLA restriction of myelin basic protein-specific T-cell clones derived from MS patients. Cell. Immunol. 1990;129:189–198. doi: 10.1016/0008-8749(90)90197-y. [DOI] [PubMed] [Google Scholar]
  28. Jouvenne P., Richardson C.D., Schreiber S.S., Lai M.M.C., Talbot P.J. Sequence analysis of the membrane protein gene of human coronavirus 229E. Virology. 1990;174:608–612. doi: 10.1016/0042-6822(90)90115-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kyte J., Doolittle R.F. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 1982;157:105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  30. Lennon V.A., Wilks A.V., Carnegie P.R. Immunologic properties of the main encephalitogenic peptide from the basic protein of human myelin. J. Immunol. 1970;105:1223–1230. [PubMed] [Google Scholar]
  31. Li X., Rhode S.L. Nonstructural protein NS2 of parvovirus H-1 is required for efficient viral protein synthesis and virus production in rat cells in vivo and in vitro. Virology. 1991;184:117–130. doi: 10.1016/0042-6822(91)90828-y. [DOI] [PubMed] [Google Scholar]
  32. Macnaughton M.R. The polypeptides of human and mouse coronaviruses. Arch. Virol. 1980;63:75–80. doi: 10.1007/BF01320763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Martenson R. Myelin basic protein speciation. Prog. Clin. Biol. Res. 1983;146:511–521. [PubMed] [Google Scholar]
  34. McIntosh K., Chao R.K., Krause H.E., Wasil R., Mocega H.E., Mufson M.A. Coronavirus infection in acute lower respiratory tract disease of infants. J. Inf. Dis. 1974;139:502–510. doi: 10.1093/infdis/130.5.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Murray RS., MacMillan B., Cabirac G., Burks J.S. Detection of coronavirus RNA in CNS tissue of multiple sclerosis and control patients. In: Cavanagh D., Brown T.D.K., editors. Coronaviruses and Their Diseases. Vol. 276. Plenum; New York: 1990. pp. 505–510. (Advances in Experimental Medicine and Biology). [DOI] [PubMed] [Google Scholar]
  36. Niesters H.G.M., Zijderveld A.J., Seifert W.F., Lenstra J.A., Bleumink-Pluym N.M.C., Horzinek M.C., Van der Zeijst B.A.M. Infectious bronchitis virus RNA D encodes three potential translation products. Nucl. Acids Res. 1986;14:3144. doi: 10.1093/nar/14.7.3144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Oldstone M.B.A. Molecular mimicry and autoimmune disease. Cell. 1987;50:819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  38. Ota K., Matsui M., Milford E.L., Mackin G.A., Weiner H.L., Hafler D.A. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature (Lond.) 1990;346:183–187. doi: 10.1038/346183a0. [DOI] [PubMed] [Google Scholar]
  39. Parker S.E., Gallagher T.M., Buchmeier M.J. Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus. Virology. 1989;173:664–673. doi: 10.1016/0042-6822(89)90579-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Raabe T., Siddell S.G. Nucleotide sequence of the gene encoding the membrane protein of human coronavirus 229E. Arch. Virol. 1989;107:323–328. doi: 10.1007/BF01317928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Raabe T., Siddell S. Nucleotide sequence of the human coronavirus HCV 229E mRNA 4 and mRNA 5 unique regions. Nucl. Acids Res. 1989;17:6387. doi: 10.1093/nar/17.15.6387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Raabe T., Schelle-Prinz B., Siddell S.G. Nucleotide sequence of the gene encoding the spike glycoprotein of human coronavirus HCV 229E. J. Gen. Virol. 1990;71:1065–1073. doi: 10.1099/0022-1317-71-5-1065. [DOI] [PubMed] [Google Scholar]
  43. Rasschaert D., Gelfi J., Laude H. Enteric coronavirus TGEV: partial sequence of the genomic RNA, its organization and expression. Biochimie. 1987;69:591–600. doi: 10.1016/0300-9084(87)90178-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Reddehase M.J., Rothbard J.B., Koszinowski U.H. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature (Lond.) 1989;337:651–653. doi: 10.1038/337651a0. [DOI] [PubMed] [Google Scholar]
  46. Resta S., Luby J.P., Rosenfeld C.R., Siegel J.D. Isolation and propagation of a human enteric coronavirus. Science. 1985;229:978–981. doi: 10.1126/science.2992091. [DOI] [PubMed] [Google Scholar]
  47. Rhode S.L. Both excision and replication of cloned autonomous parvovirus DNA require the NS1 (rep) protein. J. Virol. 1989;63:4249–4256. doi: 10.1128/jvi.63.10.4249-4256.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Richert J.R., Robinson E.D., Deibler G.E., Martenson R.E., Dragovic L.J., Kies M.W. Human cytotoxic T-cell recognition of a synthetic peptide of myelin basic protein. Ann. Neurol. 1989;26:342–346. doi: 10.1002/ana.410260306. [DOI] [PubMed] [Google Scholar]
  49. Roth HJ., Kronquist K.E., Kerlero de Rosbo N., Crandall B.F., Campagnoni A.T. Evidence for the expression of four myelin basic protein variants in the developing human spinal cord through cDNA cloning. J. Neurosci. Res. 1987;17:321–328. doi: 10.1002/jnr.490170402. [DOI] [PubMed] [Google Scholar]
  50. Saiki R.K., Gelfand D.H., Stoffel S., Scharf S.J., Higuchi R., Horn G.T., Mullis K.B., Erlich H.A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988;239:487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  51. Salmi A., Ziola B., Hovi T., Reunanen M. Antibodies to coronaviruses OC43 and 229E in multiple sclerosis patients. Neurology. 1982;32:292–295. doi: 10.1212/wnl.32.3.292. [DOI] [PubMed] [Google Scholar]
  52. Sanger F., Nicklen S., Coulson A.R. Vol. 74. 1977. DNA sequencing with chain-terminating inhibitors; pp. 5463–5469. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Schmidt O.W., Kenny G.E. Polypeptides and functions of antigens from human coronaviruses 229E and OC43. Infect. Immun. 1982;35:515–522. doi: 10.1128/iai.35.2.515-522.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Schreiber S.S., Kamahora T., Lai M.M.C. Sequence analysis of the nucleocapsid protein gene of human coronavirus 229E. Virology. 1989;169:142–151. doi: 10.1016/0042-6822(89)90050-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Schwarz B., Routledge E., Siddell S.G. Murine coronavirus nonstructural protein ns2 is not essential for virus replication in transformed cells. J. Virol. 1990;64:4784–4791. doi: 10.1128/jvi.64.10.4784-4791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Shieh C.-K., Lee H.-J., Yokomori K., La Monica N., Makino S., Lai M.M.C. Identification of a new transcriptional initiation site and the corresponding functional gene 2b in the murine coronavirus RNA genome. J. Virol. 1989;63:3729–3736. doi: 10.1128/jvi.63.9.3729-3736.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Skinner M.A., Siddell S.G. Coding sequence of coronavirus MHV-JHM mRNA 4. J. Gen. Virol. 1985;66:593–596. doi: 10.1099/0022-1317-66-3-593. [DOI] [PubMed] [Google Scholar]
  58. Skinner M.A., Ebner D., Siddell S.G. Coronavirus MHV-JHM mRNA 5 has a sequence arrangement which potentially allows translation of a second, downstream open reading frame. J. Gen. Virol. 1985;66:581–592. doi: 10.1099/0022-1317-66-3-581. [DOI] [PubMed] [Google Scholar]
  59. 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]
  60. Sturman L.S., Ricard C.S., Holmes K.V. Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90K cleavage fragments. J. Virol. 1985;56:904–911. doi: 10.1128/jvi.56.3.904-911.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Taguchi F., Fleming J.O. Comparison of six different murine coronavirus JHM variants by monoclonal antibodies against the E2 glycoprotein. Virology. 1987;169:233–235. doi: 10.1016/0042-6822(89)90061-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Takahashi N., Roach A., Teplow D.B., Prusiner S.B., Hood L. Cloning and characterization of the myelin basic protein gene from mouse: one gene can encoded both 14 kD and 18.5 kD MBPs by alternate use of exons. Cell. 1985;42:139–148. doi: 10.1016/s0092-8674(85)80109-4. [DOI] [PubMed] [Google Scholar]
  63. Tanaka R., Iwasaki Y., Koprowski H. Intracisternal virus-like particles in brain of a multiple sclerosis patient. J. Neurol. Sci. 1976;28:121–126. doi: 10.1016/0022-510X(76)90053-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Watanabe R., Wege H., Ter Meulen V. Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis. Nature (Lond.) 1983;305:150–153. doi: 10.1038/305150a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wege H., Siddell S., Ter Meulen V. The biology and pathogenesis of coronaviruses. Curr. Top. Microbiol. Immunol. 1982;99:165–200. doi: 10.1007/978-3-642-68528-6_5. [DOI] [PubMed] [Google Scholar]
  66. Weiss S.R., Leibowitz J.L. Comparison of the RNAs of murine and human coronaviruses. In: Ter Meulen V., Siddell S., Wege H., editors. Biochemistry and Biology of Coronaviruses. Vol. 142. Plenum; New York: 1981. pp. 245–259. (Advances in Experimental Medicine and Biology). [DOI] [PubMed] [Google Scholar]
  67. Wesley R.D., Cheung A.K., Michael D.D., Woods R.D. Nucleotide sequence of coronavirus TGEV genomic RNA: evidence for 3 mRNA species between the peplomer and matrix protein genes. Virus Res. 1989;13:87–100. doi: 10.1016/0168-1702(89)90008-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Yokomori K., Lai M.M.C. Mouse hepatitis virus S RNA sequence reveals that nonstructural proteins ns4 and ns5a are not essential for murine coronavirus replication. J. Virol. 1991;65:5605–5608. doi: 10.1128/jvi.65.10.5605-5608.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Yokomori K., Banner L.R., Lai M.M.C. Heterogeneity of gene expression of the hemagglutinin-esterase (HE) protein of murine coronaviruses. Virology. 1991;183:647–657. doi: 10.1016/0042-6822(91)90994-M. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Zuker M., Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucl. Acids Res. 1981;9:133–148. doi: 10.1093/nar/9.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Virus Research are provided here courtesy of Elsevier

RESOURCES