Synthesis and Quality Control of Viral Membrane Proteins

  • C. Maggioni
  • I. Braakman
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 285)


Viruses use the host cellular machinery to translate viral proteins. Similar to cellular proteins directed to the secretory pathway, viral (glyco)proteins are synthesized on polyribosomes and targeted to the endoplasmic reticulum (ER). For viruses that encode polyproteins, folding of the individual proteins of the precursor often is coordinated. Translocation and the start of folding coincide and are assisted by cellular folding factors present in the lumen of the ER. The protein concentration a newborn protein finds in this compartment is enormous (hundreds of mg/ml) and the action of molecular chaperones is essential to prevent aggregation. Viral envelope proteins also undergo the cellular quality control mechanisms, which ensure, with variable stringency, that only proteins with the correct structure will proceed through the secretory pathway. Proteins that are misfolded, or not yet folded, are retained in the ER until they reach the native conformation or until their retrotranslocation into the cytosol for degradation. Peculiar characteristic of viruses is their ability to interfere with the cellular machinery to ensure virus production and, moreover, to pass through the body unobserved by the host immune system. This section describes some mechanisms of genetic variation and viral immune evasion that involve the secretory pathway.


Major Histocompatibility Complex Class Cystic Fibrosis Transmembrane Conductance Regulator Unfold Protein Response Protein Disulfide Isomerase Disulfide Bond Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alberini CM, P Bet, C Milstein and R Sitia (1990) Secretion of immunoglobulin M assembly intermediates in the presence of reducing agents. Nature 347(6292):485–7CrossRefPubMedGoogle Scholar
  2. Andersson H, BU Barth, M Ekstrom and H Garoff (1997) Oligomerization-dependent folding of the membrane fusion protein of Semliki Forest virus. J Virol 71(12):9654–63PubMedGoogle Scholar
  3. Anelli T, M Alessio, A Mezghrani, T Simmen, F Talamo, A Bachi and R Sitia (2002) ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J 21(4): 835–44CrossRefPubMedGoogle Scholar
  4. Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181(96): 223–30PubMedGoogle Scholar
  5. Benham AM, A Cabibbo, A Fassio, N Bulleid, R Sitia and I Braakman (2000) The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lα. EMBO J 19(17): 4493–502CrossRefPubMedGoogle Scholar
  6. Bennett EM, JR Bennink, JW Yewdell and FM Brodsky (1999) Cutting edge: adenovirus E19 has two mechanisms for affecting class I MHC expression. J Immunol 162(9): 5049–52PubMedGoogle Scholar
  7. Berman PW, WM Nunes and OK Haffar (1988) Expression of membrane-associated and secreted variants of gp160 of human immunodeficiency virus type 1 in vitro and in continuous cell lines. J Virol 62(9): 3135–42PubMedGoogle Scholar
  8. Blagoveshchenskaya AD, L Thomas, SF Feliciangeli, CH Hung and G Thomas (2002) HIV-1 Nef downregulates MHC-I by a PACS-1-and PI3K-regulated ARF6 endocytic pathway. Cell 111(6): 853–66Google Scholar
  9. Braakman I, J Helenius and A Helenius (1992) Manipulating disulfide bond formation and protein folding in the endoplasmic reticulum. EMBO J 11(5): 1717–22PubMedGoogle Scholar
  10. Braakman, I., D. Hebert. Disulfide (-SS-) bond formation overview. In: Current Protocols in Protein Science, Chapter 14.1 (eds. J. Coligan, B. Dunn, H. Ploegh, D. Speicher, P. Wingfield; John Wiley and Sons, Inc, New York, 1996): 14.1.1–14.1.15Google Scholar
  11. Braakman I and E van Anken (2000) Folding of viral envelope glycoproteins in the endoplasmic reticulum. Traffic 1(7): 533–9CrossRefPubMedGoogle Scholar
  12. Brodsky JL and AA McCracken (1999) ER protein quality control and proteasome-mediated protein degradation. Semin Cell Dev Biol 10(5): 507–13CrossRefPubMedGoogle Scholar
  13. Bu G, HJ Geuze, GJ Strous and AL Schwartz (1995) 39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein. EMBO J 14(10): 2269–80PubMedGoogle Scholar
  14. Cabibbo A, M Pagani, M Fabbri, M Rocchi, MR Farmery, NJ Bulleid and R Sitia (2000) ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol Chem 275(7): 4827–33CrossRefPubMedGoogle Scholar
  15. Carleton M, H Lee, M Mulvey and DT Brown (1997) Role of glycoprotein PE2 in formation and maturation of the Sindbis virus spike. J Virol 71(2): 1558–66PubMedGoogle Scholar
  16. Cocquerel L, JC Meunier, A Op de Beeck, D Bonte, C Wychowski and J Dubuisson (2001) Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2. J Gen Virol 82(7): 1629–35PubMedGoogle Scholar
  17. Cox JH, JR Bennink and JW Yewdell (1991) Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation. J Exp Med 174(6): 1629–37CrossRefPubMedGoogle Scholar
  18. Danilczyk UG, MF Cohen-Doyle and DB Williams (2000) Functional relationship between calreticulin, calnexin, and the endoplasmic reticulum luminal domain of calnexin. J Biol Chem 275(17): 13089–97CrossRefPubMedGoogle Scholar
  19. Doms RW, RA Lamb, JK Rose and A Helenius (1993) Folding and assembly of viral membrane proteins. Virology 193(2): 545–62CrossRefPubMedGoogle Scholar
  20. Duvet S, A Op De Beeck, L Cocquerel, C Wychowski, R Cacan and J Dubuisson (2002) Glycosylation of the hepatitis C virus envelope protein E1 occurs post-translationally in a mannosylphosphoryldolichol-deficient CHO mutant cell line. Glycobiology 12(2): 95–101CrossRefPubMedGoogle Scholar
  21. Ellgaard L, P Bettendorff, D Braun, T Herrmann, F Fiorito, I Jelesarov, P Guntert, A Helenius and K Wuthrich (2002) NMR structures of 36 and 73-residue fragments of the calreticulin P-domain. J Mol Biol 322(4): 773–84CrossRefPubMedGoogle Scholar
  22. Ellgaard L and A Helenius (2001) ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol 13(4): 431–7CrossRefPubMedGoogle Scholar
  23. Ellgaard L, M Molinari and A Helenius (1999) Setting the standards: quality control in the secretory pathway. Science 286(5446): 1882–8CrossRefPubMedGoogle Scholar
  24. Ellgaard L, R Riek, D Braun, T Herrmann, A Helenius and K Wuthrich (2001) Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment. FEBS Lett 488(1–2): 69–73CrossRefPubMedGoogle Scholar
  25. Ellis RJ (2001) Macromolecular crowding: an important but neglected aspect of the intracellular environment. Curr Opin Struct Biol 11(1): 114–9CrossRefPubMedGoogle Scholar
  26. Fischer PB, GB Karlsson, TD Butters, RA Dwek and FM Platt (1996) n-Butyldeoxyno-jirimycin-mediated inhibition of human immunodeficiency virus entry correlates with changes in antibody recognition of the V1/V2 region of gp120. J Virol 70(10): 7143–52PubMedGoogle Scholar
  27. Fischer WB and MS Sansom (2002) Viral ion channels: structure and function. Biochim Biophys Acta 1561(1): 27–45PubMedGoogle Scholar
  28. Fra AM, C Fagioli, D Finazzi, R Sitia and CM Alberini (1993) Quality control of ER synthesized proteins: an exposed thiol group as a three-way switch mediating assembly, retention and degradation. EMBO J 12(12): 4755–61PubMedGoogle Scholar
  29. Frand AR and CA Kaiser (1998) The ERO1 gene of yeast is required for oxidation of protein dithiols in the endoplasmic reticulum. Mol Cell 1(2): 161–70CrossRefPubMedGoogle Scholar
  30. Frand AR and CA Kaiser (1999) Ero1p oxidizes protein disulfide isomerase in a pathway for disulfide bond formation in the endoplasmic reticulum. Mol Cell 4(4): 469–77CrossRefPubMedGoogle Scholar
  31. Freedman RB, P Klappa and LW Ruddock (2002) Protein disulfide isomerases exploit synergy between catalytic and specific binding domains. EMBO Rep 3(2):136–40CrossRefPubMedGoogle Scholar
  32. Frickel EM, R Riek, I Jelesarov, A Helenius, K Wuthrich and L Ellgaard (2002) TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain. Proc Natl Acad Sci U S A 99(4): 1954–9CrossRefPubMedGoogle Scholar
  33. Friedlander R, E Jarosch, J Urban, C Volkwein and T Sommer (2000) A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nat Cell Biol 2(7): 379–84CrossRefPubMedGoogle Scholar
  34. Fujita K, S Omura and J Silver (1997) Rapid degradation of CD4 in cells expressing human immunodeficiency virus type 1 Env and Vpu is blocked by proteasome inhibitors. J Gen Virol 78(3): 619–25PubMedGoogle Scholar
  35. Gerber J, U Muhlenhoff, G Hofhaus, R Lill and T Lisowsky (2001) Yeast ERV2p is the first microsomal FAD-linked sulfhydryl oxidase of the Erv1p/Alrp protein family. J Biol Chem 276(26): 23486–91CrossRefPubMedGoogle Scholar
  36. Gorlich D and TA Rapoport (1993) Protein translocation into proteoliposomes reconstituted from purified components of the endoplasmic reticulum membrane. Cell 75(4): 615–30CrossRefPubMedGoogle Scholar
  37. Gothel SF and MA Marahiel (1999) Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts. Cell Mol Life Sci 55(3): 423–36CrossRefPubMedGoogle Scholar
  38. Haigh NG and AE Johnson (2002) A new role for BiP: closing the aqueous translocon pore during protein integration into the ER membrane. J Cell Biol 156(2): 261–70CrossRefPubMedGoogle Scholar
  39. Hammond C, I Braakman and A Helenius (1994) Role of N-linked oligosaccharide recognition, glucose trimming, and calnexin in glycoprotein folding and quality control. Proc Natl Acad Sci U S A 91(3): 913–7PubMedGoogle Scholar
  40. Harding HP, M Calfon, F Urano, I Novoa and D Ron (2002) Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol 18:575–99CrossRefPubMedGoogle Scholar
  41. Hartmann E, D Gorlich, S Kostka, A Otto, R Kraft, S Knespel, E Burger, TA Rapoport and S Prehn (1993) A tetrameric complex of membrane proteins in the endoplasmic reticulum. Eur J Biochem 214(2): 375–81CrossRefPubMedGoogle Scholar
  42. Hauri H, C Appenzeller, F Kuhn and O Nufer (2000) Lectins and traffic in the secretory pathway. FEBS Lett 476(1–2): 32–7CrossRefPubMedGoogle Scholar
  43. Hebert DN, JX Zhang, W Chen, B Foellmer and A Helenius (1997) The number and location of glycans on influenza hemagglutinin determine folding and association with calnexin and calreticulin. J Cell Biol 139(3): 613–23CrossRefPubMedGoogle Scholar
  44. Hegde NR, RA Tomazin, TW Wisner, C Dunn, JM Boname, DM Lewinsohn and DC Johnson (2002) Inhibition of HLA-DR assembly, transport, and loading by human cytomegalovirus glycoprotein US3: a novel mechanism for evading major histocompatibility complex class II antigen presentation. J Virol 76(21): 10929–41CrossRefPubMedGoogle Scholar
  45. Hegde RS, S Voigt, TA Rapoport and VR Lingappa (1998) TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum. Cell 92(5): 621–31CrossRefPubMedGoogle Scholar
  46. Helenius J, DT Ng, CL Marolda, P Walter, MA Valvano and M Aebi (2002) Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein. Nature 415(6870): 447–50CrossRefPubMedGoogle Scholar
  47. Hengel H, JO Koopmann, T Flohr, W Muranyi, E Goulmy, GJ Hammerling, UH Koszinowski and F Momburg (1997) A viral ER-resident glycoprotein inactivates the MHC-encoded peptide transporter. Immunity 6(5): 623–32CrossRefPubMedGoogle Scholar
  48. Hesketh JE and IF Pryme (1991) Interaction between mRNA, ribosomes and the cytoskeleton. Biochem J 277(1): 1–10PubMedGoogle Scholar
  49. Hewitt EW, SS Gupta and PJ Lehner (2001) The human cytomegalovirus gene product US6 inhibits ATP binding by TAP. EMBO J 20(3): 387–96CrossRefPubMedGoogle Scholar
  50. Hobbs HH, MS Brown and JL Goldstein (1992) Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1(6): 445–66CrossRefPubMedGoogle Scholar
  51. Holtappels R, D Thomas, J Podlech, G Geginat, HP Steffens and MJ Reddehase (2000) The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells. J Virol 74(4): 1871–84CrossRefPubMedGoogle Scholar
  52. Hwang C, AJ Sinskey and HF Lodish (1992) Oxidized redox state of glutathione in the endoplasmic reticulum. Science 257(5076): 1496–502PubMedGoogle Scholar
  53. Imperiali B and KW Rickert (1995) Conformational implications of asparagine-linked glycosylation. Proc Natl Acad Sci U S A 92(1): 97–101PubMedGoogle Scholar
  54. Jakob CA, D Bodmer, U Spirig, P Battig, A Marcil, D Dignard, JJ Bergeron, DY Thomas and M Aebi (2001) Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation in yeast. EMBO Rep 2(5): 423–30PubMedGoogle Scholar
  55. Johnson AE and MA van Waes (1999) The translocon: a dynamic gateway at the ER membrane. Annu Rev Cell Dev Biol 15:799–842CrossRefPubMedGoogle Scholar
  56. Kerkau T, I Bacik, JR Bennink, JW Yewdell, T Hunig, A Schimpl and U Schubert (1997) The human immunodeficiency virus type 1 (HIV-1) Vpu protein interferes with an early step in the biosynthesis of major histocompatibility complex (MHC) class I molecules. J Exp Med 185(7): 1295–305CrossRefPubMedGoogle Scholar
  57. Land A, D Zonneveld and I Braakman (2003) Folding of HIV-1 envelope glycoprotein involves extensive isomerization of disulfide bonds and conformation-dependent signal peptide cleavage. FASEB J in pressGoogle Scholar
  58. Leonchiks A, V Stavropoulou, A Sharipo and MG Masucci (2002) Inhibition of ubiquitin-dependent proteolysis by a synthetic glycine-alanine repeat peptide that mimics an inhibitory viral sequence. FEBS Lett 522(1–3): 93–8CrossRefPubMedGoogle Scholar
  59. Levitskaya J, A Sharipo, A Leonchiks, A Ciechanover and MG Masucci (1997) Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. Proc Natl Acad Sci USA 94(23): 12616–21CrossRefPubMedGoogle Scholar
  60. Li Y, L Luo, DY Thomas and CY Kang (1994) Control of expression, glycosylation, and secretion of HIV-1 gp120 by homologous and heterologous signal sequences. Virology 204(1): 266–78CrossRefPubMedGoogle Scholar
  61. Lorenz IC, SL Allison, FX Heinz and A Helenius (2002) Folding and dimerization of tick-borne encephalitis virus envelope proteins prM and E in the endoplasmic reticulum. J Virol 76(11): 5480–91CrossRefPubMedGoogle Scholar
  62. Ma Y and LM Hendershot (2001) The unfolding tale of the unfolded protein response. Cell 107(7): 827–30CrossRefPubMedGoogle Scholar
  63. Matlack KE, W Mothes and TA Rapoport (1998) Protein translocation: tunnel vision. Cell 92(3): 381–90CrossRefPubMedGoogle Scholar
  64. Merola M, M Brazzoli, F Cocchiarella, JM Heile, A Helenius, AJ Weiner, M Houghton and S Abrignani (2001) Folding of hepatitis C virus E1 glycoprotein in a cell-free system. J Virol 75(22): 11205–17CrossRefPubMedGoogle Scholar
  65. Mezghrani A, A Fassio, A Benham, T Simmen, I Braakman and R Sitia (2001) Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J 20(22): 6288–96CrossRefPubMedGoogle Scholar
  66. Michalak JP, C Wychowski, A Choukhi, JC Meunier, S Ung, CM Rice and J Dubuisson (1997) Characterization of truncated forms of hepatitis C virus glycoproteins. J Gen Virol 78(9): 2299–306PubMedGoogle Scholar
  67. Molinari M, C Galli, V Piccaluga, M Pieren and P Paganetti (2002) Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER. J Cell Biol 158(2): 247–57CrossRefPubMedGoogle Scholar
  68. Molinari M and A Helenius (1999) Glycoproteins form mixed disulphides with oxidoreductases during folding in living cells. Nature 402(6757): 90–3CrossRefPubMedGoogle Scholar
  69. Molinari M and A Helenius (2000) Chaperone selection during glycoprotein translocation into the endoplasmic reticulum. Science 288(5464): 331–3CrossRefPubMedGoogle Scholar
  70. Momburg F and P Tan (2002) Tapasin-the keystone of the loading complex optimizing peptide binding by MHC class I molecules in the endoplasmic reticulum. Mol Immunol 39(3–4): 217–33CrossRefPubMedGoogle Scholar
  71. Nagata K (1996) Hsp47: a collagen-specific molecular chaperone. Trends Biochem Sci 21(1): 22–6CrossRefPubMedGoogle Scholar
  72. Nakatsukasa K, S Nishikawa, N Hosokawa, K Nagata and T Endo (2001) Mnl1p, an alpha-mannosidase-like protein in yeast Saccharomyces cerevisiae, is required for endoplasmic reticulum-associated degradation of glycoproteins. J Biol Chem 276(12): 8635–8CrossRefPubMedGoogle Scholar
  73. Noiva R (1999) Protein disulfide isomerase: the multifunctional redox chaperone of the endoplasmic reticulum. Semin Cell Dev Biol 10(5): 481–93CrossRefPubMedGoogle Scholar
  74. Norgaard P, V Westphal, C Tachibana, L Alsoe, B Holst and JR Winther (2001) Functional differences in yeast protein disulfide isomerases. J Cell Biol 152(3): 553–62CrossRefPubMedGoogle Scholar
  75. Pagani M, M Fabbri, C Benedetti, A Fassio, S Pilati, NJ Bulleid, A Cabibbo and R Sitia (2000) Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response. J Biol Chem 275(31): 23685–92CrossRefPubMedGoogle Scholar
  76. Parodi AJ (2000) Protein glucosylation and its role in protein folding. Annu Rev Biochem 69:69–93CrossRefPubMedGoogle Scholar
  77. Patel J, AH Patel and J McLauchlan (2001) The transmembrane domain of the hepatitis C virus E2 glycoprotein is required for correct folding of the E1 glycoprotein and native complex formation. Virology 279(1): 58–68CrossRefPubMedGoogle Scholar
  78. Patil C and P Walter (2001) Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol 13(3): 349–55CrossRefPubMedGoogle Scholar
  79. Paul M and MA Jabbar (1997) Phosphorylation of both phosphoacceptor sites in the HIV-1 Vpu cytoplasmic domain is essential for Vpu-mediated ER degradation of CD4. Virology 232(1): 207–16CrossRefPubMedGoogle Scholar
  80. Peterson JR, A Ora, PN Van and A Helenius (1995) Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins. Mol Biol Cell 6(9): 1173–84PubMedGoogle Scholar
  81. Piguet V, YL Chen, A Mangasarian, M Foti, JL Carpentier and D Trono (1998) Mechanism of Nef-induced CD4 endocytosis: Nef connects CD4 with the mu chain of adaptor complexes. EMBO J 17(9): 2472–81CrossRefPubMedGoogle Scholar
  82. Pollard MG, KJ Travers and JS Weissman (1998) Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum. Mol Cell 1(2): 171–82CrossRefPubMedGoogle Scholar
  83. Rehm A, P Stern, HL Ploegh and D Tortorella (2001) Signal peptide cleavage of a type I membrane protein, HCMV US11, is dependent on its membrane anchor. EMBO J 20(7): 1573–82CrossRefPubMedGoogle Scholar
  84. Rhee SS and JW Marsh (1994) Human immunodeficiency virus type 1 Nef-induced down-modulation of CD4 is due to rapid internalization and degradation of surface CD4. J Virol 68(8): 5156–63PubMedGoogle Scholar
  85. Schrag JD, JJ Bergeron, Y Li, S Borisova, M Hahn, DY Thomas and M Cygler (2001) The structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol Cell 8(3): 633–44CrossRefPubMedGoogle Scholar
  86. Schwartz O, V Marechal, S Le Gall, F Lemonnier and JM Heard (1996) Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 2(3): 338–42CrossRefPubMedGoogle Scholar
  87. Senkevich TG, CL White, EV Koonin and B Moss (2002) Complete pathway for protein disulfide bond formation encoded by poxviruses. Proc Natl Acad Sci USA 99(10): 6667–72CrossRefPubMedGoogle Scholar
  88. Sevier CS, JW Cuozzo, A Vala, F Aslund and CA Kaiser (2001) A flavoprotein oxidase defines a new endoplasmic reticulum pathway for biosynthetic disulphide bond formation. Nat Cell Biol 3(10): 874–82CrossRefPubMedGoogle Scholar
  89. Sitia R, M Neuberger, C Alberini, P Bet, A Fra, C Valetti, G Williams and C Milstein (1990) Developmental regulation of IgM secretion: the role of the carboxy-terminal cysteine. Cell 60(5): 781–90CrossRefPubMedGoogle Scholar
  90. Su HL, CL Liao and YL Lin (2002) Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response. J Virol 76(9):4162–71CrossRefPubMedGoogle Scholar
  91. Tardif KD, K Mori and A Siddiqui (2002) Hepatitis C virus subgenomic replicons induce endoplasmic reticulum stress activating an intracellular signaling pathway. J Virol 76(15): 7453–9CrossRefPubMedGoogle Scholar
  92. Tasab M, MR Batten and NJ Bulleid (2000) Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen. EMBO J 19(10): 2204–11CrossRefPubMedGoogle Scholar
  93. Tomazin R, J Boname, NR Hegde, DM Lewinsohn, Y Altschuler, TR Jones, P Cresswell, JA Nelson, SR Riddell and DC Johnson (1999) Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. Nat Med 5(9): 1039–43CrossRefPubMedGoogle Scholar
  94. Tortorella D, BE Gewurz, MH Furman, DJ Schust and HL Ploegh (2000) Viral subversion of the immune system. Annu Rev Immunol 18:861–926CrossRefPubMedGoogle Scholar
  95. Travers KJ, CK Patil, L Wodicka, DJ Lockhart, JS Weissman and P Walter (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101(3): 249–58CrossRefPubMedGoogle Scholar
  96. Tsai B, Y Ye and TA Rapoport (2002) Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat Rev Mol Cell Biol 3(4): 246–55CrossRefPubMedGoogle Scholar
  97. Tu BP, SC Ho-Schleyer, KJ Travers and JS Weissman (2000) Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science 290(5496): 1571–4CrossRefPubMedGoogle Scholar
  98. Tu BP and JS Weissman (2002) The FAD-and O2-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum. Mol Cell 10(5):983–94CrossRefPubMedGoogle Scholar
  99. van der Wal FJ, M Kikkert and E Wiertz (2002) The HCMV gene products US2 and US11 target MHC class I molecules for degradation in the cytosol. Curr Top Microbiol Immunol 269:37–55PubMedGoogle Scholar
  100. Vossen MT, EM Westerhout, C Soderberg-Naucler and EJ Wiertz (2002) Viral immune evasion: a masterpiece of evolution. Immunogenetics 54(8): 527–42CrossRefPubMedGoogle Scholar
  101. Wang L and B Dobberstein (1999) Oligomeric complexes involved in translocation of proteins across the membrane of the endoplasmic reticulum. FEBS Lett 457(3): 316–22CrossRefPubMedGoogle Scholar
  102. Ward CL and RR Kopito (1994) Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J Biol Chem 269(41): 25710–8PubMedGoogle Scholar
  103. Wiertz EJ, TR Jones, L Sun, M Bogyo, HJ Geuze and HL Ploegh (1996) The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84(5): 769–79CrossRefPubMedGoogle Scholar
  104. Williams M, JF Roeth, MR Kasper, RI Fleis, CG Przybycin and KL Collins (2002) Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking. J Virol 76(23): 12173–84CrossRefPubMedGoogle Scholar
  105. Wolin SL and P Walter (1988) Ribosome pausing and stacking during translation of a eukaryotic mRNA. EMBO J 7(11): 3559–69PubMedGoogle Scholar
  106. York IA, C Roop, DW Andrews, SR Riddell, FL Graham and DC Johnson (1994) A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77(4): 525–35CrossRefPubMedGoogle Scholar
  107. Zhang Y, G Nijbroek, ML Sullivan, AA McCracken, SC Watkins, S Michaelis and JL Brodsky (2001) Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast. Mol Biol Cell 12(5): 1303–14PubMedGoogle Scholar
  108. Ziegler H, R Thale, P Lucin, W Muranyi, T Flohr, H Hengel, H Farrell, W Rawlinson and UH Koszinowski (1997) A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments. Immunity 6(1):57–66CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • C. Maggioni
    • 1
  • I. Braakman
    • 1
  1. 1.University of UtrechtUtrechtThe Netherlands

Personalised recommendations