1887

Abstract

Live attenuated strains of human cytomegalovirus are under development as vaccines to prevent birth defects resulting from congenital infections. These strains encode four proteins that inhibit surface expression of MHC class I, presumably to evade cytotoxic T-cell recognition and, perhaps, attenuate induction of immunity. To initiate studies of the role of class I down-regulation on congenital infection and vaccine efficacy, the ability of guinea pig cytomegalovirus to down-regulate class I was examined. Surface class I was specifically down-regulated on infected cells up to 8-fold. Sensitivity to UV irradiation and insensitivity to a viral DNA synthesis inhibitor revealed that immediate early or early viral gene(s) are responsible. Identification of these genes will permit future experiments to evaluate the role of class I down-regulation in congenital cytomegalovirus disease and its impact on vaccine efficacy. These findings should be pertinent to understanding human cytomegalovirus disease and may help guide the design of candidate vaccines.

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2003-01-01
2020-01-22
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References

  1. Abbate, J., Lacayo, J. C., Prichard, M., Pari, G. & McVoy, M. A. ( 2001; ). Bifunctional protein conferring enhanced green fluorescence and puromycin resistance. Biotechniques 31, 336–340.
    [Google Scholar]
  2. Abendroth, A., Lin, I., Slobedman, B., Ploegh, H. & Arvin, A. M. ( 2001; ). Varicella-zoster virus retains major histocompatibility complex class I proteins in the Golgi compartment of infected cells. J Virol 75, 4878–4888.[CrossRef]
    [Google Scholar]
  3. Ahn, K., Angulo, A., Ghazal, P., Peterson, P. A., Yang, Y. & Fruh, K. ( 1996; ). Human cytomegalovirus inhibits antigen presentation by a sequential multistep process. Proc Natl Acad Sci U S A 93, 10990–10995.[CrossRef]
    [Google Scholar]
  4. Ahn, K., Gruhler, A., Galocha, B., Jones, T. R., Wiertz, E. J., Ploegh, H. L., Peterson, P. A., Yang, Y. & Fruh, K. ( 1997; ). The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Immunity 6, 613–621.[CrossRef]
    [Google Scholar]
  5. Ambagala, A. P., Hinkley, S. & Srikumaran, S. ( 2000; ). An early pseudorabies virus protein down-regulates porcine MHC class I expression by inhibition of transporter associated with antigen processing (TAP). J Immunol 164, 93–99.[CrossRef]
    [Google Scholar]
  6. Balfour, H. H., Jr Sachs, G. W., Welo, P., Gehrz, R. C., Simmons, R. L. & Najarian, J. S. ( 1984; ). Cytomegalovirus vaccine in renal transplant candidates: progress report of a randomized, placebo-controlled, double-blind trial. Birth Defects Orig Artic Ser 20, 289–304.
    [Google Scholar]
  7. Barnes, P. D. & Grundy, J. E. ( 1992; ). Down-regulation of the class I HLA heterodimer and β2-microglobulin on the surface of cells infected with cytomegalovirus. J Gen Virol 73, 2395–2403.[CrossRef]
    [Google Scholar]
  8. Bia, F. J., Griffith, B. P., Tarsio, M. & Hsiung, G. D. ( 1980; ). Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus. J Infect Dis 142, 732–738.[CrossRef]
    [Google Scholar]
  9. Bia, F. J., Lucia, H. L., Fong, C. K., Tarsio, M. & Hsiung, G. D. ( 1982; ). Effects of vaccination on cytomegalovirus-associated interstitial pneumonia in strain 2 guinea pigs. J Infect Dis 145, 742–747.[CrossRef]
    [Google Scholar]
  10. Campbell, A. E. & Slater, J. S. ( 1994; ). Down-regulation of major histocompatibility complex class I synthesis by murine cytomegalovirus early gene expression. J Virol 68, 1805–1811.
    [Google Scholar]
  11. Cohen, J. I. ( 1998; ). Infection of cells with varicella-zoster virus down-regulates surface expression of class I major histocompatibility complex antigens. J Infect Dis 177, 1390–1393.[CrossRef]
    [Google Scholar]
  12. del Val, M., Hengel, H., Hacker, H., Hartlaub, U., Ruppert, T., Lucin, P. & Koszinowski, U. H. ( 1992; ). 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 176, 729–738.[CrossRef]
    [Google Scholar]
  13. Fong, C. K., Lucia, H., Bia, F. J. & Hsiung, G. D. ( 1983; ). Histopathologic and ultrastructural studies of disseminated cytomegalovirus infection in strain 2 guinea pigs. Lab Invest 49, 183–194.
    [Google Scholar]
  14. Fortunato, E. A., Dell’Aquila, M. L. & Spector, D. H. ( 2000; ). Specific chromosome 1 breaks induced by human cytomegalovirus. Proc Nat Acad Sci U S A 97, 853–858.[CrossRef]
    [Google Scholar]
  15. Fowler, K. B., Stagno, S., Pass, R. F., Britt, W. J., Boll, T. J. & Alford, C. A. ( 1992; ). The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med 326, 663–667.[CrossRef]
    [Google Scholar]
  16. Gonczol, E. & Plotkin, S. ( 2001; ). Development of a cytomegalovirus vaccine: lessons from recent clinical trials. Expert Opin Biol Ther 1, 401–412.[CrossRef]
    [Google Scholar]
  17. Griffith, B. P. & Aquino-de Jesus, M. J. ( 1991; ). Guinea pig model of congenital cytomegalovirus infection. Transplant Proc 23, 29–31.
    [Google Scholar]
  18. Griffith, B. P., Lucia, H. L., Bia, F. J. & Hsiung, G. D. ( 1981; ). Cytomegalovirus-induced mononucleosis in guinea pigs. Infect Immun 32, 857–863.
    [Google Scholar]
  19. Griffith, B. P., Chen, M. & Isom, H. C. ( 1990; ). Role of primary and secondary maternal viremia in transplacental guinea pig cytomegalovirus transfer. J Virol 64, 1991–1997.
    [Google Scholar]
  20. Hallermalm, K., Seki, K., Wei, C., Castelli, C., Rivoltini, L., Kiessling, R. & Levitskaya, J. ( 2001; ). Tumor necrosis factor-alpha induces coordinated changes in major histocompatibility class I presentation pathway, resulting in increased stability of class I complexes at the cell surface. Blood 98, 1108–1115.[CrossRef]
    [Google Scholar]
  21. Hariharan, M. J., Nataraj, C. & Srikumaran, S. ( 1993; ). Down regulation of murine MHC class I expression by bovine herpesvirus 1. Viral Immunol 6, 273–284.[CrossRef]
    [Google Scholar]
  22. Harrison, C. J., Britt, W. J., Chapman, N. M., Mullican, J. & Tracy, S. ( 1995; ). Reduced congenital cytomegalovirus (CMV) infection after maternal immunization with a guinea pig CMV glycoprotein before gestational primary CMV infection in the guinea pig model. J Infect Dis 172, 1212–1220.[CrossRef]
    [Google Scholar]
  23. Hill, A., Jugovic, P., York, I., Russ, G., Bennink, J., Yewdell, J., Ploegh, H. & Johnson, D. ( 1995; ). Herpes simplex virus turns off the TAP to evade host immunity. Nature 375, 411–415.[CrossRef]
    [Google Scholar]
  24. Hinkley, S., Hill, A. B. & Srikumaran, S. ( 1998; ). Bovine herpesvirus-1 infection affects the peptide transport activity in bovine cells. Virus Res 53, 91–96.[CrossRef]
    [Google Scholar]
  25. Hirata, Y., Kondo, K. & Yamanishi, K. ( 2001; ). Human herpesvirus 6 downregulates major histocompatibility complex class I in dendritic cells. J Med Virol 65, 576–583.[CrossRef]
    [Google Scholar]
  26. Hudson, A. W., Howley, P. M. & Ploegh, H. L. ( 2001; ). A human herpesvirus 7 glycoprotein, U21, diverts major histocompatibility complex class I molecules to lysosomes. J Virol 75, 12347–12358.[CrossRef]
    [Google Scholar]
  27. Hunt, H. D., Lupiani, B., Miller, M. M., Gimeno, I., Lee, L. F. & Parcells, M. S. ( 2001; ). Marek's disease virus down-regulates surface expression of MHC (B Complex) class I (BF) glycoproteins during active but not latent infection of chicken cells. Virology 282, 198–205.[CrossRef]
    [Google Scholar]
  28. Ishido, S., Wang, C., Lee, B. S., Cohen, G. B. & Jung, J. U. ( 2000; ). Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins. J Virol 74, 5300–5309.[CrossRef]
    [Google Scholar]
  29. Jing, X. J., Kalman-Maltese, V., Cao, X., Yang, Q. & Trempe, J. P. ( 2001; ). Inhibition of adenovirus cytotoxicity, replication, and E2a gene expression by adeno-associated virus. Virology 291, 140–151.[CrossRef]
    [Google Scholar]
  30. Johnson, K. P. & Connor, W. S. ( 1979; ). Guinea pig cytomegalovirus: transplacental transmission. Brief report. Arch Virol 59, 263–267.[CrossRef]
    [Google Scholar]
  31. Jones, T. R. & Sun, L. ( 1997; ). Human cytomegalovirus US2 destabilizes major histocompatibility complex class I heavy chains. J Virol 71, 2970–2979.
    [Google Scholar]
  32. Jones, T. R., Hanson, L. K., Sun, L., Slater, J. S., Stenberg, R. M. & Campbell, A. E. ( 1995; ). Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains. J Virol 69, 4830–4841.
    [Google Scholar]
  33. Jones, T. R., Wiertz, E. J., Sun, L., Fish, K. N., Nelson, J. A. & Ploegh, H. L. ( 1996; ). Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proc Natl Acad Sci U S A 93, 11327–11333.[CrossRef]
    [Google Scholar]
  34. Jugovic, P., Hill, A. M., Tomazin, R., Ploegh, H. & Johnson, D. C. ( 1998; ). Inhibition of major histocompatibility complex class I antigen presentation in pig and primate cells by herpes simplex virus type 1 and 2 ICP47. J Virol 72, 5076–5084.
    [Google Scholar]
  35. Kemble, G., Duke, G., Winter, R. & Spaete, R. ( 1996; ). Defined large-scale alterations of the human cytomegalovirus genome constructed by cotransfection of overlapping cosmids. J Virol 70, 2044–2048.
    [Google Scholar]
  36. Ledbetter, J. A. & Herzenberg, L. A. ( 1979; ). Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev 47, 63–90.[CrossRef]
    [Google Scholar]
  37. Liu, Y. & Biegalke, B. J. ( 2001; ). Characterization of a cluster of late genes of guinea pig cytomegalovirus. Virus Genes 23, 247–256.[CrossRef]
    [Google Scholar]
  38. Lorenzo, M. E., Ploegh, H. L. & Tirabassi, R. S. ( 2001; ). Viral immune evasion strategies and the underlying cell biology. Semin Immunol 13, 1–9.[CrossRef]
    [Google Scholar]
  39. McVoy, M. A., Nixon, D. E. & Adler, S. P. ( 1997; ). Circularization and cleavage of guinea pig cytomegalovirus genomes. J Virol 71, 4209–4217.
    [Google Scholar]
  40. Nankervis, G. A. & Kumar, M. L. ( 1978; ). Diseases produced by cytomegaloviruses. Med Clin North Am 62, 1021–1035.
    [Google Scholar]
  41. Nataraj, C., Eidmann, S., Hariharan, M. J., Sur, J. H., Perry, G. A. & Srikumaran, S. ( 1997; ). Bovine herpesvirus 1 downregulates the expression of bovine MHC class I molecules. Viral Immunol 10, 21–34.[CrossRef]
    [Google Scholar]
  42. Plotkin, S. A., Starr, S. E., Friedman, H. M. & 7 other authors ( 1991; ). Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial. Ann Intern Med 114, 525–531.[CrossRef]
    [Google Scholar]
  43. Plotkin, S. A., Higgins, R., Kurtz, J. B., Morris, P. J., Campbell, D. A., Jr, Shope, T. C., Spector, S. A. & Dankner, W. M. ( 1994; ). Multicenter trial of Towne strain attenuated virus vaccine in seronegative renal transplant recipients. Transplantation 58, 1176–1178.[CrossRef]
    [Google Scholar]
  44. Rescigno, M., Citterio, S., Thery, C., Rittig, M., Medaglini, D., Pozzi, G., Amigorena, S. & Ricciardi-Castagnoli, P. ( 1998; ). Bacteria-induced neo-biosynthesis, stabilization, and surface expression of functional class I molecules in mouse dendritic cells. Proc Natl Acad Sci U S A 95, 5229–5234.[CrossRef]
    [Google Scholar]
  45. Reusch, U., Muranyi, W., Lucin, P., Burgert, H. G., Hengel, H. & Koszinowski, U. H. ( 1999; ). A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. EMBO J 18, 1081–1091.[CrossRef]
    [Google Scholar]
  46. Sambrook, J., Fritsch, E. F. & Maniatis, T. ( 1989; ). Molecular Cloning, a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  47. Sato, H., Inaba, T. & Kamiya, H. ( 1997; ). Production of murine monoclonal antibodies to guinea pig leukocytes and immunohistochemistry of guinea pig skin exposed to Schistosoma mansoni. Hybridoma 16, 529–536.[CrossRef]
    [Google Scholar]
  48. Schäfer, H., Bartels, T., Hahn, G., Otto, A. & Burger, R. ( 1999; ). T-cell-activating monoclonal antibodies, reacting with both leukocytes and erythrocytes, recognize the guinea pig Thy-1 differentiation antigen: characterization and cloning of guinea pig CD90. Cell Immunol 197, 116–128.[CrossRef]
    [Google Scholar]
  49. Schleiss, M. R., Bourne, N., Jensen, N. J., Bravo, F. & Bernstein, D. I. ( 2000; ). Immunogenicity evaluation of DNA vaccines that target guinea pig cytomegalovirus proteins glycoprotein B and UL83. Viral Immunol 13, 155–167.[CrossRef]
    [Google Scholar]
  50. Steinmassl, M. & Hamprecht, K. ( 1994; ). Double fluorescence analysis of human cytomegalovirus (HCMV) infected human fibroblast cultures by flow cytometry: increase of class I MHC expression on uninfected cells and decrease on infected cells. Arch Virol 135, 75–87.[CrossRef]
    [Google Scholar]
  51. Stevenson, P. G., Efstathiou, S., Doherty, P. C. & Lehner, P. J. ( 2000; ). Inhibition of MHC class I-restricted antigen presentation by γ2-herpesviruses. Proc Natl Acad Sci U S A 97, 8455–8460.[CrossRef]
    [Google Scholar]
  52. Tomazin, R., van Schoot, N. E., Goldsmith, K., Jugovic, P., Sempe, P., Fruh, K. & Johnson, D. C. ( 1998; ). Herpes simplex virus type 2 ICP47 inhibits human TAP but not mouse TAP. J Virol 72, 2560–2563.
    [Google Scholar]
  53. Wiertz, E. J., Jones, T. R., Sun, L., Bogyo, M., Geuze, H. J. & Ploegh, H. L. ( 1996; ). The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84, 769–779.[CrossRef]
    [Google Scholar]
  54. Yamashita, Y., Shimokata, K., Mizuno, S., Yamaguchi, H. & Nishiyama, Y. ( 1993; ). Down-regulation of the surface expression of class I MHC antigens by human cytomegalovirus. Virol 193, 727–736.[CrossRef]
    [Google Scholar]
  55. York, I. A., Roop, C., Andrews, D. W., Riddell, S. R., Graham, F. L. & Johnson, D. C. ( 1994; ). A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77, 525–535.[CrossRef]
    [Google Scholar]
  56. Zeidler, R., Eissner, G., Meissner, P., Uebel, S., Tampe, R., Lazis, S. & Hammerschmidt, W. ( 1997; ). Downregulation of TAP1 in B lymphocytes by cellular and Epstein–Barr virus-encoded interleukin-10. Blood 90, 2390–2397.
    [Google Scholar]
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