Skip to main content

Advertisement

Log in

Nucleocytoplasmic shuttling and CRM1-dependent MHC class I peptide presentation of human cytomegalovirus pp65

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

The phosphoprotein 65 (pp65) of human cytomegalovirus is a prominent target of the antiviral CD8 T lymphocyte response. This study focused on investigating the properties of pp65 that render it a privileged antigen. It was found that pp65 was metabolically stable. The tegument protein was introduced into MHC class I presentation following its delivery via non-replicating dense bodies. No ubiquitination was found on particle-associated pp65. Proof was obtained that pp65 was a nucleocytoplasmic shuttle protein, using heterokaryon analyses. Based on this finding, inhibition experiments showed that presentation of particle-derived pp65 by HLA-A2 was sensitive to the impairment of the CRM1-mediated nuclear export pathway. The data support the idea that particle-derived pp65 can serve as a nuclear reservoir for proteasomal processing and MHC class I presentation, following its CRM1-dependent nuclear export. The presentation of pp65-derived peptides was also impaired by CRM1-inhibition following de novo synthesis of the tegument protein. However, pp65 protein levels were also reduced when blocking CRM1-mediated export after transient expression. This indicated that pp65 expression rather than direct interference with its own nuclear export was responsible for its reduced presentation in this case. The functionality of CRM1-mediated nuclear export is thus important for the presentation of pp65-derived peptides in the context of MHC class I on organ cells, both after exogenous uptake and after de novo synthesis of the tegument protein, but different mechanisms may account for either case.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

The references marked with an asterisk result from the work within project part E7 of the collaborative research center (SFB) 490.

  1. Thomas S, Herr W (2011) Natural and adoptive T-cell immunity against herpes family viruses after allogeneic hematopoietic stem cell transplantation. Immunotherapy 3:771–788

    Article  PubMed  CAS  Google Scholar 

  2. Reusser P, Riddell SR, Meyers JD, Greenberg PD (1991) Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 78:1373–1380

    PubMed  CAS  Google Scholar 

  3. Reddehase MJ, Mutter W, Münch K, Bühring HJ, Koszinowski UH (1987) CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. J Virol 61:3102–3108

    PubMed  CAS  Google Scholar 

  4. Holtappels R, Böhm V, Podlech J, Reddehase MJ (2008) CD8 T-cell-based immunotherapy of cytomegalovirus infection: “proof of concept” provided by the murine model. Med Microbiol Immunol 197:125–134

    Article  PubMed  Google Scholar 

  5. Podlech J, Holtappels R, Wirtz N, Steffens HP, Reddehase MJ (1998) Reconstitution of CD8 T cells is essential for the prevention of multiple-organ cytomegalovirus histopathology after bone marrow transplantation. J Gen Virol 79:2099–2104

    PubMed  CAS  Google Scholar 

  6. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR (1995) Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 333:1038–1044

    Article  PubMed  CAS  Google Scholar 

  7. Einsele H, Kapp M, Grigoleit GU (2008) CMV-specific T cell therapy. Blood Cells Mol Dis 40:71–75

    Article  PubMed  CAS  Google Scholar 

  8. Moss P, Rickinson A (2005) Cellular immunotherapy for viral infection after HSC transplantation. Nat Rev Immunol 5:9–20

    Article  PubMed  CAS  Google Scholar 

  9. Borysiewicz LK, Hickling JK, Graham S, Sinclair J, Cranage MP, Smith GL, Sissons JG (1988) Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. J Exp Med 168:919–931

    Article  PubMed  CAS  Google Scholar 

  10. McLaughlin-Taylor E, Pande H, Forman SJ, Tanamachi B, Li CR, Zaia JA, Greenberg PD, Riddell SR (1994) Identification of the major late human cytomegalovirus matrix protein pp 65 as a target antigen for CD8+ virus-specific cytotoxic T lymphocytes. J Med Virol 43:103–110

    Article  PubMed  CAS  Google Scholar 

  11. Boppana SB, Britt WJ (1996) Recognition of human cytomegalovirus gene products by HCMV- specific cytotoxic T cells. Virology 222:293–296. doi:10.1006/viro.1996.0424

    Article  PubMed  CAS  Google Scholar 

  12. Elkington R, Walker S, Crough T, Menzies M, Tellam J, Bharadwaj M, Khanna R (2003) Ex vivo profiling of CD8+ -T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers. J Virol 77:5226–5240

    Article  PubMed  CAS  Google Scholar 

  13. Manley TJ, Luy L, Jones T, Boeckh M, Mutimer H, Riddell SR (2004) Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection. Blood 104:1075–1082

    Article  PubMed  CAS  Google Scholar 

  14. Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, Sleath PR, Grabstein KH, Hosken NA, Kern F, Nelson JA, Picker LJ (2005) Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 202:673–685

    Article  PubMed  CAS  Google Scholar 

  15. Rüger B, Klages S, Walla B, Albrecht J, Fleckenstein B, Tomlinson P, Barrell B (1987) Primary structure and transcription of the genes coding for the two virion phosphoproteins pp 65 and pp 71 of human cytomegalovirus. J Virol 61:446–453

    PubMed  Google Scholar 

  16. Roby C, Gibson W (1986) Characterization of phosphoproteins and protein kinase activity of virions, noninfectious enveloped particles, and dense bodies of human cytomegalovirus. J Virol 59:714–727

    PubMed  CAS  Google Scholar 

  17. Varnum SM, Streblow DN, Monroe ME, Smith P, Auberry KJ, Pasa-Tolic L, Wang D, Camp DG, Rodland K, Wiley S, Britt W, Shenk T, Smith RD, Nelson JA (2004) Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol 78:10960–10966

    Article  PubMed  CAS  Google Scholar 

  18. Grefte, JM, van-der-Gun, BT, Schmolke S, van-der-Giessen M, van-Son WJ, Plachter, B, Jahn G, The TH (1992) The lower matrix protein pp65 is the principal viral antigen present in peripheral blood leukocytes during an active cytomegalovirus infection. J Gen Virol 73:2923–2932

    Google Scholar 

  19. Schmolke S, Kern HF, Drescher P, Jahn G, Plachter B (1995) The dominant phosphoprotein pp 65 (UL83) of human cytomegalovirus is dispensable for growth in cell culture. J Virol 69:5959–5968

    PubMed  CAS  Google Scholar 

  20. Chevillotte M, Landwehr S, Linta L, Frascaroli G, Luske A, Buser C, Mertens T, von EJ (2009) Major tegument protein pp 65 of human cytomegalovirus is required for the incorporation of pUL69 and pUL97 into the virus particle and for viral growth in macrophages. J Virol 83:2480–2490

    Article  PubMed  CAS  Google Scholar 

  21. Gallina A, Simoncini L, Garbelli S, Percivalle E, Pedrali-Noy G, Lee KS, Erikson RL, Plachter B, Gerna G, Milanesi G (1999) Polo-like kinase 1 as a target for human cytomegalovirus pp 65 lower matrix protein. J Virol 73:1468–1478

    PubMed  CAS  Google Scholar 

  22. To A, Bai Y, Shen A, Gong H, Umamoto S, Lu S, Liu F (2011) Yeast two hybrid analyses reveal novel binary interactions between human cytomegalovirus-encoded virion proteins. PLoS ONE 6:e17796

    Article  PubMed  CAS  Google Scholar 

  23. Phillips SL, Bresnahan WA (2011) Identification of binary interactions between human cytomegalovirus virion proteins. J Virol 85:440–447

    Article  PubMed  CAS  Google Scholar 

  24. *Becke S, Fabre-Mersseman V, Aue S, Auerochs S, Sedmak T, Wolfrum U, Strand D, Marschall M, Plachter B, Reyda S (2010) Modification of the major tegument protein pp 65 of human cytomegalovirus inhibits virus growth and leads to the enhancement of a protein complex with pUL69 and pUL97 in infected cells. J Gen Virol 91:2531–2541

    Article  PubMed  CAS  Google Scholar 

  25. Cristea IM, Moorman NJ, Terhune SS, Cuevas CD, O’Keefe ES, Rout MP, Chait BT, Shenk T (2010) Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J Virol 84:7803–7814

    Article  PubMed  CAS  Google Scholar 

  26. Gilbert MJ, Riddell SR, Plachter B, Greenberg PD (1996) Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature 383:720–722

    Article  PubMed  CAS  Google Scholar 

  27. *Odeberg J, Plachter B, Branden L, Soderberg-Naucler C (2003) Human cytomegalovirus protein pp 65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR alpha-chain. Blood 101:4870–4877

    Article  PubMed  CAS  Google Scholar 

  28. *Arnon TI, Achdout H, Levi O, Markel G, Saleh N, Katz G, Gazit R, Gonen-Gross T, Hanna J, Nahari E, Porgador A, Honigman A, Plachter B, Mevorach D, Wolf DG, Mandelboim O (2005) Inhibition of the NKp30 activating receptor by pp 65 of human cytomegalovirus. Nat Immunol 6:515–523

    Article  PubMed  CAS  Google Scholar 

  29. Sanchez V, Mahr JA, Orazio NI, Spector DH (2007) Nuclear export of the human cytomegalovirus tegument protein pp 65 requires cyclin-dependent kinase activity and the Crm1 exporter. J Virol 81:11730–11736

    Article  PubMed  CAS  Google Scholar 

  30. *Besold K, Frankenberg N, Pepperl-Klindworth S, Kuball J, Theobald M, Hahn G, Plachter B (2007) Processing and MHC class I presentation of human cytomegalovirus pp 65-derived peptides persist despite gpUS2-11-mediated immune evasion. J Gen Virol 88:1429–1439

    Article  PubMed  CAS  Google Scholar 

  31. Borst EM, Hahn G, Koszinowski UH, Messerle M (1999) Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J Virol 73:8320–8329

    PubMed  CAS  Google Scholar 

  32. Falk CS, Mach M, Schendel DJ, Weiss EH, Hilgert I, Hahn G (2002) NK cell activity during human cytomegalovirus infection is dominated by US2-11-mediated HLA class I down-regulation. J Immunol 169:3257–3266

    PubMed  CAS  Google Scholar 

  33. Andreoni M, Faircloth M, Vugler L, Britt WJ (1989) A rapid microneutralization assay for the measurement of neutralizing antibody reactive with human cytomegalovirus. J Virol Methods 23:157–167

    Article  PubMed  CAS  Google Scholar 

  34. *Pepperl S, Münster J, Mach M, Harris JR, Plachter B (2000) Dense bodies of human cytomegalovirus induce both humoral and cellular immune responses in the absence of viral gene expression. J Virol 74:6132–6146

    Article  PubMed  CAS  Google Scholar 

  35. Lischka P, Rosorius O, Trommer E, Stamminger T (2001) A novel transferable nuclear export signal mediates CRM1-independent nucleocytoplasmic shuttling of the human cytomegalovirus transactivator protein pUL69. EMBO J 20:7271–7283

    Google Scholar 

  36. Jahn G, Harthus HP, Bröker M, Borisch B, Platzer B, Plachter B (1990) Generation and application of a monoclonal antibody raised against a recombinant cytomegalovirus-specific polypeptide. Klin Wochenschr 68:1003–1007

    Article  PubMed  CAS  Google Scholar 

  37. Miyahira Y, Murata K, Rodriguez D, Rodriguez JR, Esteban M, Rodrigues MM, Zavala F (1995) Quantification of antigen specific CD8+ T cells using an ELISPOT assay. J Immunol Methods 181:45–54

    Article  PubMed  CAS  Google Scholar 

  38. *Frankenberg N, Pepperl-Klindworth S, Meyer RG, Plachter B (2002) Identification of a conserved HLA-A2-restricted decapeptide from the IE1 protein (pUL123) of human cytomegalovirus. Virology 295:208–216

    Article  PubMed  CAS  Google Scholar 

  39. Urban M, Klein M, Britt WJ, Hassfurther E, Mach M (1996) Glycoprotein H of human cytomegalovirus is a major antigen for the neutralizing humoral immune response. J Gen Virol 77(Pt 7):1537–1547

    Article  PubMed  CAS  Google Scholar 

  40. Schmolke S, Drescher P, Jahn G, Plachter B (1995) Nuclear targeting of the tegument protein pp 65 (UL83) of human cytomegalovirus: an unusual bipartite nuclear localization signal functions with other portions of the protein to mediate its efficient nuclear transport. J Virol 69:1071–1078

    PubMed  CAS  Google Scholar 

  41. Shirangi TR, Zaika A, Moll UM (2002) Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage. FASEB J 16:420–422

    PubMed  CAS  Google Scholar 

  42. Roth J, Dobbelstein M (1997) Export of hepatitis B virus RNA on a Rev-like pathway: inhibition by the regenerating liver inhibitory factor IkappaB alpha. J Virol 71:8933–8939

    PubMed  CAS  Google Scholar 

  43. Pepperl S, Benninger-Döring G, Modrow S, Wolf H, Jilg W (1998) Immediate-early transactivator Rta of Epstein-Barr virus (EBV) shows multiple epitopes recognized by EBV-specific cytotoxic T lymphocytes. J Virol 72:8644–8649

    PubMed  CAS  Google Scholar 

  44. Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–87

    Article  PubMed  CAS  Google Scholar 

  45. Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (1994) Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761–771

    Article  PubMed  CAS  Google Scholar 

  46. Momburg F, Hämmerling GJ (1998) Generation and TAP-mediated transport of peptides for major histocompatibility complex class I molecules. Adv Immunol 68:191–256

    Article  PubMed  CAS  Google Scholar 

  47. Kloetzel PM (2001) Antigen processing by the proteasome. Nat Rev Mol Cell Biol 2:179–187

    Article  PubMed  CAS  Google Scholar 

  48. Beninga, J and Goldberg, AL (1998) Function of the proteasome in antigen presentation In: Peters J.M., Harris, JR, and Finley, D (eds) Ubiquitin and the Biology of the Cell, Plenum Press, New York, 191-222

  49. *Pepperl-Klindworth S, Frankenberg N, Riegler S, Plachter B (2003) Protein delivery by subviral particles of human cytomegalovirus. Gene Ther 10:278–284

    Article  PubMed  CAS  Google Scholar 

  50. Yewdell JW (2011) DRiPs solidify: progress in understanding endogenous MHC class I antigen processing. Trends Immunol 32:548–558

    Article  PubMed  CAS  Google Scholar 

  51. Frankenberg N, Besold K, Pepperl-Klindworth S, Lischka P, Kuball J, Theobald M, Plachter B (2005) MHC-class I presentation of peptides from the immunodominant HCMV tegument protein pp 65 is dependent on Crm1 mediated nuclear export 30th International Herpesvirus Workshop. Turku, Finnland

    Google Scholar 

  52. Pinol-Roma S, Dreyfuss G (1992) Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature 355:730–732

    Article  PubMed  CAS  Google Scholar 

  53. Wen W, Meinkoth JL, Tsien RY, Taylor SS (1995) Identification of a signal for rapid export of proteins from the nucleus. Cell 82:463–473

    Article  PubMed  CAS  Google Scholar 

  54. Fischer U, Huber J, Boelens WC, Mattaj IW, Luhrmann R (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82:475–483

    Article  PubMed  CAS  Google Scholar 

  55. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, Nishida E (1997) CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390:308–311

    Article  PubMed  CAS  Google Scholar 

  56. Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90:1051–1060

    Article  PubMed  CAS  Google Scholar 

  57. Wolff B, Sanglier JJ, Wang Y (1997) Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem Biol 4:139–147

    Article  PubMed  CAS  Google Scholar 

  58. Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner EP, Wolff B, Yoshida M, Horinouchi S (1999) Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci USA 96:9112–9117

    Article  PubMed  CAS  Google Scholar 

  59. Shida H (2012) Role of Nucleocytoplasmic RNA transport during the life cycle of retroviruses. Front Microbiol 3:179

    Google Scholar 

  60. Freedman DA, Levine AJ (1998) Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol 18:7288–7293

    Google Scholar 

  61. Waller EC, Day E, Sissons JG, Wills MR (2008) Dynamics of T cell memory in human cytomegalovirus infection. Med Microbiol Immunol 197:83–96

    Article  PubMed  Google Scholar 

  62. Kern F, Bunde T, Faulhaber N, Kiecker F, Khatamzas E, Rudawski IM, Pruss A, Gratama JW, Volkmer-Engert R, Ewert R, Reinke P, Volk HD, Picker LJ (2002) Cytomegalovirus (CMV) phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed individuals. J Infect Dis 185:1709–1716

    Article  PubMed  CAS  Google Scholar 

  63. Bunde T, Kirchner A, Hoffmeister B, Habedank D, Hetzer R, Cherepnev G, Proesch S, Reinke P, Volk HD, Lehmkuhl H, Kern F (2005) Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J Exp Med 201:1031–1036

    Article  PubMed  CAS  Google Scholar 

  64. Peggs KS, Thomson K, Samuel E, Dyer G, Armoogum J, Chakraverty R, Pang K, Mackinnon S, Lowdell MW (2011) Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis 52:49–57

    Article  PubMed  CAS  Google Scholar 

  65. McDonald B, Martin-Serrano J (2009) No strings attached: the ESCRT machinery in viral budding and cytokinesis. J Cell Sci 122:2167–2177

    Article  PubMed  CAS  Google Scholar 

  66. Harrison MS, Schmitt PT, Pei Z, Schmitt AP (2012) Role of ubiquitin in parainfluenza virus 5 particle formation. J Virol 86:3474–3485

    Article  PubMed  CAS  Google Scholar 

  67. Prichard MN, Britt WJ, Daily SL, Hartline CB, Kern ER (2005) Human cytomegalovirus UL97 Kinase is required for the normal intranuclear distribution of pp 65 and virion morphogenesis. J Virol 79:15494–15502

    Article  PubMed  CAS  Google Scholar 

  68. Toth Z, Lischka P, Stamminger T (2006) RNA-binding of the human cytomegalovirus transactivator protein UL69, mediated by arginine-rich motifs, is not required for nuclear export of unspliced RNA. Nucleic Acids Res 34:1237–1249

    Article  PubMed  CAS  Google Scholar 

  69. Lischka P, Toth Z, Thomas M, Mueller R, Stamminger T (2006) The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA. Mol Cell Biol 26:1631–1643

    Article  PubMed  CAS  Google Scholar 

  70. Lahaye F, Lespinasse F, Staccini P, Palin L, Paquis-Flucklinger V, Santucci-Darmanin S (2010) hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization. Nucleic Acids Res 38:3655–3671

    Article  PubMed  CAS  Google Scholar 

  71. Cheong JK, Gunaratnam L, Hsu SI (2008) CRM1-mediated nuclear export is required for 26 S proteasome-dependent degradation of the TRIP-Br2 proto-oncoprotein. J Biol Chem 283:11661–11676

    Article  PubMed  CAS  Google Scholar 

  72. Ivanova IA, Dagnino L (2007) Activation of p38- and CRM1-dependent nuclear export promotes E2F1 degradation during keratinocyte differentiation. Oncogene 26:1147–1154

    Article  PubMed  CAS  Google Scholar 

  73. Knauer SK, Carra G, Stauber RH (2005) Nuclear export is evolutionarily conserved in CVC paired-like homeobox proteins and influences protein stability, transcriptional activation, and extracellular secretion. Mol Cell Biol 25:2573–2582

    Article  PubMed  CAS  Google Scholar 

  74. Nguyen KT, Holloway MP, Altura RA (2012) The CRM1 nuclear export protein in normal development and disease Int. J Biochem Mol Biol 3:137–151

    CAS  Google Scholar 

  75. Thomas M, Reuter N, Stamminger T (2013) Multifaceted regulation of huma cytomegalovirus gene expression. In: Reddehase MJ (ed) Cytomegaloviruses: from molecular pathogenesis to intervention. Caister Academic Press, Norfolk

  76. Makler O, Oved K, Netzer N, Wolf D, Reiter Y (2010) Direct visualization of the dynamics of antigen presentation in human cells infected with cytomegalovirus revealed by antibodies mimicking TCR specificity. Eur J Immunol 40:1552–1565

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The technical assistance of Manuela Starke is gratefully acknowledged. We thank Katrin Besold for a critical review of the manuscript. We are indebted to Ute Moll (New York, NY) for the HTLV-1 plasmid pFlagNLSRex, to Eva Borst, Martin Messerle (Hannover, Germany) and Gabi Hahn (Ingolstadt, Germany) for BAC-clones and to William Britt (Birmingham, AL) for monoclonal antibodies. Dr. Jochen Beninga was involved in the initial experiments of this work. This work was supported by the Deutsche Forschungsgemeinschaft, SFB 490, individual project E7 (B.P.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bodo Plachter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frankenberg, N., Lischka, P., Pepperl-Klindworth, S. et al. Nucleocytoplasmic shuttling and CRM1-dependent MHC class I peptide presentation of human cytomegalovirus pp65. Med Microbiol Immunol 201, 567–579 (2012). https://doi.org/10.1007/s00430-012-0269-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-012-0269-7

Keywords

Navigation