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. 1994 Dec;68(12):7757–7765. doi: 10.1128/jvi.68.12.7757-7765.1994

Identification and expression of a murine cytomegalovirus early gene coding for an Fc receptor.

R Thäle 1, P Lucin 1, K Schneider 1, M Eggers 1, U H Koszinowski 1
PMCID: PMC237237  PMID: 7966565

Abstract

Several herpesviruses, including cytomegalovirus, induce receptors for the Fc domain of murine immunoglobulin G (IgG) molecules. Viral genes coding for these receptors have been characterized only for alphaherpesviruses. In this report, we describe a new approach that led to the identification of an Fc receptor (FcR) of murine cytomegalovirus (MCMV). The Fc fragment of IgG precipitated glycoproteins (gp) of 86 to 88 and 105 kDa from MCMV-infected cells. Deglycosylation by endoglycosidase F resulted in a protein with a molecular mass of 64 kDa. Injection of complete MCMV DNA or of DNA fragments, and the subsequent testing of cytoplasmic binding of IgG by immunofluorescence microscopy, was used to search for the coding region in the MCMV genome. The gene was located in the HindIII J fragment, map units 0.838 to 0.846, where an open reading frame of 1,707 nucleotides predicts a gp of 569 amino acids with a calculated molecular mass of 65 kDa. The sequence of this gp is related to those of the gE proteins of herpes simplex virus type 1 and varicella-zoster virus. The defined length of the mRNA, 1,838 nucleotides, was in agreement with that of a 1.9-kb RNA expressed throughout the replication cycle, starting at the early stages of infection. Expression of the gene fcr1 by recombinant vaccinia virus resulted in the synthesis of gp86/88 and gp105, each with FcR properties, and the correct identification of the gene encoding the FcR was confirmed by the DNA injection method.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler R., Glorioso J. C., Cossman J., Levine M. Possible role of Fc receptors on cells infected and transformed by herpesvirus: escape from immune cytolysis. Infect Immun. 1978 Aug;21(2):442–447. doi: 10.1128/iai.21.2.442-447.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander S., Elder J. H. Endoglycosidases from Flavobacterium meningosepticum application to biological problems. Methods Enzymol. 1989;179:505–518. doi: 10.1016/0076-6879(89)79151-5. [DOI] [PubMed] [Google Scholar]
  3. Baucke R. B., Spear P. G. Membrane proteins specified by herpes simplex viruses. V. Identification of an Fc-binding glycoprotein. J Virol. 1979 Dec;32(3):779–789. doi: 10.1128/jvi.32.3.779-789.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bell S., Cranage M., Borysiewicz L., Minson T. Induction of immunoglobulin G Fc receptors by recombinant vaccinia viruses expressing glycoproteins E and I of herpes simplex virus type 1. J Virol. 1990 May;64(5):2181–2186. doi: 10.1128/jvi.64.5.2181-2186.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burton D. R., Woof J. M. Human antibody effector function. Adv Immunol. 1992;51:1–84. doi: 10.1016/s0065-2776(08)60486-1. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. D'Souza S. E., Ginsberg M. H., Plow E. F. Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. Trends Biochem Sci. 1991 Jul;16(7):246–250. doi: 10.1016/0968-0004(91)90096-e. [DOI] [PubMed] [Google Scholar]
  8. Del Val M., Münch K., Reddehase M. J., Koszinowski U. H. Presentation of CMV immediate-early antigen to cytolytic T lymphocytes is selectively prevented by viral genes expressed in the early phase. Cell. 1989 Jul 28;58(2):305–315. doi: 10.1016/0092-8674(89)90845-3. [DOI] [PubMed] [Google Scholar]
  9. Del Val M., Schlicht H. J., Ruppert T., Reddehase M. J., Koszinowski U. H. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991 Sep 20;66(6):1145–1153. doi: 10.1016/0092-8674(91)90037-y. [DOI] [PubMed] [Google Scholar]
  10. Dowler K. W., Veltri R. W. In vitro neutralization of HSV-2: inhibition by binding of normal IgG and purified Fc to virion Fc receptor (FcR). J Med Virol. 1984;13(3):251–259. doi: 10.1002/jmv.1890130307. [DOI] [PubMed] [Google Scholar]
  11. Dubin G., Basu S., Mallory D. L., Basu M., Tal-Singer R., Friedman H. M. Characterization of domains of herpes simplex virus type 1 glycoprotein E involved in Fc binding activity for immunoglobulin G aggregates. J Virol. 1994 Apr;68(4):2478–2485. doi: 10.1128/jvi.68.4.2478-2485.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dubin G., Socolof E., Frank I., Friedman H. M. Herpes simplex virus type 1 Fc receptor protects infected cells from antibody-dependent cellular cytotoxicity. J Virol. 1991 Dec;65(12):7046–7050. doi: 10.1128/jvi.65.12.7046-7050.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ebeling A., Keil G. M., Knust E., Koszinowski U. H. Molecular cloning and physical mapping of murine cytomegalovirus DNA. J Virol. 1983 Sep;47(3):421–433. doi: 10.1128/jvi.47.3.421-433.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Elliott R., Clark C., Jaquish D., Spector D. H. Transcription analysis and sequence of the putative murine cytomegalovirus DNA polymerase gene. Virology. 1991 Nov;185(1):169–186. doi: 10.1016/0042-6822(91)90765-4. [DOI] [PubMed] [Google Scholar]
  15. Frank I., Friedman H. M. A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G. J Virol. 1989 Nov;63(11):4479–4488. doi: 10.1128/jvi.63.11.4479-4488.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Frey J., Einsfelder B. Induction of surface IgG receptors in cytomegalovirus-infected human fibroblasts. Eur J Biochem. 1984 Jan 2;138(1):213–216. doi: 10.1111/j.1432-1033.1984.tb07903.x. [DOI] [PubMed] [Google Scholar]
  17. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Furukawa T., Hornberger E., Sakuma S., Plotkin S. A. Demonstration of immunoglobulin G receptors induced by human cytomegalovirus. J Clin Microbiol. 1975 Oct;2(4):332–336. doi: 10.1128/jcm.2.4.332-336.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hanke T., Graham F. L., Lulitanond V., Johnson D. C. Herpes simplex virus IgG Fc receptors induced using recombinant adenovirus vectors expressing glycoproteins E and I. Virology. 1990 Aug;177(2):437–444. doi: 10.1016/0042-6822(90)90507-n. [DOI] [PubMed] [Google Scholar]
  21. Johnson D. C., Feenstra V. Identification of a novel herpes simplex virus type 1-induced glycoprotein which complexes with gE and binds immunoglobulin. J Virol. 1987 Jul;61(7):2208–2216. doi: 10.1128/jvi.61.7.2208-2216.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Johnson D. C., Frame M. C., Ligas M. W., Cross A. M., Stow N. D. Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gI. J Virol. 1988 Apr;62(4):1347–1354. doi: 10.1128/jvi.62.4.1347-1354.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jonjić S., Pavić I., Polić B., Crnković I., Lucin P., Koszinowski U. H. Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus. J Exp Med. 1994 May 1;179(5):1713–1717. doi: 10.1084/jem.179.5.1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Keller R., Peitchel R., Goldman J. N., Goldman M. An IgG-Fc receptor induced in cytomegalovirus-infected human fibroblasts. J Immunol. 1976 Mar;116(3):772–777. [PubMed] [Google Scholar]
  25. Kouzarides T., Bankier A. T., Satchwell S. C., Weston K., Tomlinson P., Barrell B. G. Sequence and transcription analysis of the human cytomegalovirus DNA polymerase gene. J Virol. 1987 Jan;61(1):125–133. doi: 10.1128/jvi.61.1.125-133.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Litwin V., Sandor M., Grose C. Cell surface expression of the varicella-zoster virus glycoproteins and Fc receptor. Virology. 1990 Sep;178(1):263–272. doi: 10.1016/0042-6822(90)90402-d. [DOI] [PubMed] [Google Scholar]
  28. Loh L. C., Balachandran N., Qualtiere L. F. Characterization of a major virion envelope glycoprotein complex of murine cytomegalovirus and its immunological cross-reactivity with human cytomegalovirus. Virology. 1988 Sep;166(1):206–216. doi: 10.1016/0042-6822(88)90162-6. [DOI] [PubMed] [Google Scholar]
  29. Mackett M., Smith G. L., Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. doi: 10.1128/jvi.49.3.857-864.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Manning W. C., Stoddart C. A., Lagenaur L. A., Abenes G. B., Mocarski E. S. Cytomegalovirus determinant of replication in salivary glands. J Virol. 1992 Jun;66(6):3794–3802. doi: 10.1128/jvi.66.6.3794-3802.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McKeating J. A., Griffiths P. D., Weiss R. A. HIV susceptibility conferred to human fibroblasts by cytomegalovirus-induced Fc receptor. Nature. 1990 Feb 15;343(6259):659–661. doi: 10.1038/343659a0. [DOI] [PubMed] [Google Scholar]
  32. Melan M. A., Sluder G. Redistribution and differential extraction of soluble proteins in permeabilized cultured cells. Implications for immunofluorescence microscopy. J Cell Sci. 1992 Apr;101(Pt 4):731–743. doi: 10.1242/jcs.101.4.731. [DOI] [PubMed] [Google Scholar]
  33. Messerle M., Bühler B., Keil G. M., Koszinowski U. H. Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3. J Virol. 1992 Jan;66(1):27–36. doi: 10.1128/jvi.66.1.27-36.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ogata M., Shigeta S. Appearance of immunoglobulin G Fc receptor in cultured human cells infected with varicella-zoster virus. Infect Immun. 1979 Nov;26(2):770–774. doi: 10.1128/iai.26.2.770-774.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Oleszak E. L., Leibowitz J. L. Immunoglobulin Fc binding activity is associated with the mouse hepatitis virus E2 peplomer protein. Virology. 1990 May;176(1):70–80. doi: 10.1016/0042-6822(90)90231-F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pierschbacher M. D., Ruoslahti E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature. 1984 May 3;309(5963):30–33. doi: 10.1038/309030a0. [DOI] [PubMed] [Google Scholar]
  37. Rahman A. A., Teschner M., Sethi K. K., Brandis H. Appearance of IgG (Fc) receptor(s) on cultured human fibroblasts infected with human cytomegalovirus. J Immunol. 1976 Jul;117(1):253–258. [PubMed] [Google Scholar]
  38. Rapp M., Lucin P., Messerle M., Loh L. C., Koszinowski U. H. Expression of the murine cytomegalovirus glycoprotein H by recombinant vaccinia virus. J Gen Virol. 1994 Jan;75(Pt 1):183–188. doi: 10.1099/0022-1317-75-1-183. [DOI] [PubMed] [Google Scholar]
  39. Rapp M., Messerle M., Bühler B., Tannheimer M., Keil G. M., Koszinowski U. H. Identification of the murine cytomegalovirus glycoprotein B gene and its expression by recombinant vaccinia virus. J Virol. 1992 Jul;66(7):4399–4406. doi: 10.1128/jvi.66.7.4399-4406.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Reddehase M. J., Keil G. M., Koszinowski U. H. The cytolytic T lymphocyte response to the murine cytomegalovirus. I. Distinct maturation stages of cytolytic T lymphocytes constitute the cellular immune response during acute infection of mice with the murine cytomegalovirus. J Immunol. 1984 Jan;132(1):482–489. [PubMed] [Google Scholar]
  41. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  42. Schowalter D. B., Sommer S. S. The generation of radiolabeled DNA and RNA probes with polymerase chain reaction. Anal Biochem. 1989 Feb 15;177(1):90–94. doi: 10.1016/0003-2697(89)90019-5. [DOI] [PubMed] [Google Scholar]
  43. Spaete R. R., Thayer R. M., Probert W. S., Masiarz F. R., Chamberlain S. H., Rasmussen L., Merigan T. C., Pachl C. Human cytomegalovirus strain Towne glycoprotein B is processed by proteolytic cleavage. Virology. 1988 Nov;167(1):207–225. doi: 10.1016/0042-6822(88)90071-2. [DOI] [PubMed] [Google Scholar]
  44. Stannard L. M., Hardie D. R. An Fc receptor for human immunoglobulin G is located within the tegument of human cytomegalovirus. J Virol. 1991 Jun;65(6):3411–3415. doi: 10.1128/jvi.65.6.3411-3415.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stürzl M., Roth W. K. "Run-off" synthesis and application of defined single-stranded DNA hybridization probes. Anal Biochem. 1990 Feb 15;185(1):164–169. doi: 10.1016/0003-2697(90)90274-d. [DOI] [PubMed] [Google Scholar]
  46. Tabor S., Richardson C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767–4771. doi: 10.1073/pnas.84.14.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Unkeless J. C., Scigliano E., Freedman V. H. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. doi: 10.1146/annurev.iy.06.040188.001343. [DOI] [PubMed] [Google Scholar]
  48. WATKINS J. F. ADSORPTION OF SENSITIZED SHEEP ERYTHROCYTES TO HELA CELLS INFECTED WITH HERPES SIMPLEX VIRUS. Nature. 1964 Jun 27;202:1364–1365. doi: 10.1038/2021364a0. [DOI] [PubMed] [Google Scholar]
  49. Westmoreland D., St Jeor S., Rapp F. The development by cytomegalovirus-infected cells of binding affinity for normal human immunoglobulin. J Immunol. 1976 Jun;116(6):1566–1570. [PubMed] [Google Scholar]
  50. Xu-Bin, Murayama T., Ishida K., Furukawa T. Characterization of IgG Fc receptors induced by human cytomegalovirus. J Gen Virol. 1989 Apr;70(Pt 4):893–900. doi: 10.1099/0022-1317-70-4-893. [DOI] [PubMed] [Google Scholar]
  51. Yamada K. M., Kennedy D. W. Dualistic nature of adhesive protein function: fibronectin and its biologically active peptide fragments can autoinhibit fibronectin function. J Cell Biol. 1984 Jul;99(1 Pt 1):29–36. doi: 10.1083/jcb.99.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Yee C., Costa J., Hamilton V., Klein G., Rabson A. S. Changes in the expression of Fc receptor produced by induction of Epstein-Barr virus in lymphoma cell lines. Virology. 1982 Jul 30;120(2):376–382. doi: 10.1016/0042-6822(82)90038-1. [DOI] [PubMed] [Google Scholar]
  53. del Val M., Hengel H., Häcker H., Hartlaub U., Ruppert T., Lucin P., Koszinowski U. H. Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. J Exp Med. 1992 Sep 1;176(3):729–738. doi: 10.1084/jem.176.3.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. van de Winkel J. G., Capel P. J. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today. 1993 May;14(5):215–221. doi: 10.1016/0167-5699(93)90166-I. [DOI] [PubMed] [Google Scholar]
  55. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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