Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment

doi:10.1084/jem.176.3.729

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by del Val, M.
	Articles by Koszinowski, U. H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by del Val, M.
	Articles by Koszinowski, U. H.

Social Bookmarking

	What's this?

ARTICLES

Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment

M del Val, H Hengel, H Hacker, U Hartlaub, T Ruppert, P Lucin and UH Koszinowski
Department of Virology, University of Ulm, Germany.

Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to the presentation by the major histocompatibility complex (MHC) class I molecule Ld of a peptide derived from MCMV IE protein pp89 (Reddehase, M.J., J. B. Rothbard, and U.H. Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides identified the pp89 peptide as the nonapeptide 168YPHFMPTNL176 (del Val, M., H.-J. Schlicht, T. Ruppert, M.J. Reddehase, and U.H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression of MCMV early genes prevents presentation of pp89 (del Val, M., K. Munch, M.J. Reddehase, and U.H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial gene lacZ by recombinant MCMV subjected antigen presentation of beta-galactosidase to the same control and excluded antigen specificity. The Ld-dependent presence of naturally processed antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the step of antigen processing. The finding that during the E phase of MCMV gene expression the MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block within the endoplasmic reticulum/cis-Golgi compartment. The failure to present antigenic peptides was explained by a general retention of nascent assembled trimolecular MHC class I complexes. Accordingly, at later stages of infection a significant decrease of surface MHC class I expression was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes endow this virus with an effective immune evasion potential. These results also indicate that the formation of the trimolecular complex of MHC class I heavy chain, beta 2-microglobulin, and the finally trimmed peptide is completed before entering the medial-Golgi compartment.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Pinto, A. K., Jamieson, A. M., Raulet, D. H., Hill, A. B. (2007). The Role of NKG2D Signaling in Inhibition of Cytotoxic T-Lymphocyte Lysis by the Murine Cytomegalovirus Immunoevasin m152/gp40. J. Virol. 81: 12564-12571 [Abstract] [Full Text]
Pinto, A. K., Munks, M. W., Koszinowski, U. H., Hill, A. B. (2006). Coordinated Function of Murine Cytomegalovirus Genes Completely Inhibits CTL Lysis.. J. Immunol. 177: 3225-3234 [Abstract] [Full Text]
Holtappels, R., Gillert-Marien, D., Thomas, D., Podlech, J., Deegen, P., Herter, S., Oehrlein-Karpi, S. A., Strand, D., Wagner, M., Reddehase, M. J. (2006). Cytomegalovirus encodes a positive regulator of antigen presentation.. J. Virol. 80: 7613-7624 [Abstract] [Full Text]
Hasan, M., Krmpotic, A., Ruzsics, Z., Bubic, I., Lenac, T., Halenius, A., Loewendorf, A., Messerle, M., Hengel, H., Jonjic, S., Koszinowski, U. H. (2005). Selective Down-Regulation of the NKG2D Ligand H60 by Mouse Cytomegalovirus m155 Glycoprotein. J. Virol. 79: 2920-2930 [Abstract] [Full Text]
Krmpotic, A., Hasan, M., Loewendorf, A., Saulig, T., Halenius, A., Lenac, T., Polic, B., Bubic, I., Kriegeskorte, A., Pernjak-Pugel, E., Messerle, M., Hengel, H., Busch, D. H., Koszinowski, U. H., Jonjic, S. (2005). NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145. J. Exp. Med. 201: 211-220 [Abstract] [Full Text]
Bubeck, A., Wagner, M., Ruzsics, Z., Lotzerich, M., Iglesias, M., Singh, I. R., Koszinowski, U. H. (2004). Comprehensive Mutational Analysis of a Herpesvirus Gene in the Viral Genome Context Reveals a Region Essential for Virus Replication. J. Virol. 78: 8026-8035 [Abstract] [Full Text]
Dorner, B. G., Smith, H. R.C., French, A. R., Kim, S., Poursine-Laurent, J., Beckman, D. L., Pingel, J. T., Kroczek, R. A., Yokoyama, W. M. (2004). Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection. J. Immunol. 172: 3119-3131 [Abstract] [Full Text]
Weber, O., Siegling, A., Friebe, A., Limmer, A., Schlapp, T., Knolle, P., Mercer, A., Schaller, H., Volk, H.-D. (2003). Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus. J. Gen. Virol. 84: 1843-1852 [Abstract] [Full Text]
Menard, C., Wagner, M., Ruzsics, Z., Holak, K., Brune, W., Campbell, A. E., Koszinowski, U. H. (2003). Role of Murine Cytomegalovirus US22 Gene Family Members in Replication in Macrophages. J. Virol. 77: 5557-5570 [Abstract] [Full Text]
Arieh, S. V.-B., Laham, N., Schechter, C., Yewdell, J. W., Coligan, J. E., Ehrlich, R. (2003). A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules. Blood 101: 2858-2864 [Abstract] [Full Text]
Lacayo, J., Sato, H., Kamiya, H., McVoy, M. A. (2003). Down-regulation of surface major histocompatibility complex class I by guinea pig cytomegalovirus. J. Gen. Virol. 84: 75-81 [Abstract] [Full Text]
LoPiccolo, D. M., Gold, M. C., Kavanagh, D. G., Wagner, M., Koszinowski, U. H., Hill, A. B. (2002). Effective Inhibition of Kb- and Db-Restricted Antigen Presentation in Primary Macrophages by Murine Cytomegalovirus. J. Virol. 77: 301-308 [Abstract] [Full Text]
Holtappels, R., Grzimek, N. K. A., Simon, C. O., Thomas, D., Dreis, D., Reddehase, M. J. (2002). Processing and Presentation of Murine Cytomegalovirus pORFm164-Derived Peptide in Fibroblasts in the Face of All Viral Immunosubversive Early Gene Functions. J. Virol. 76: 6044-6053 [Abstract] [Full Text]
Holtappels, R., Grzimek, N. K. A., Thomas, D., Reddehase, M. J. (2002). Early gene m18, a novel player in the immune response to murine cytomegalovirus. J. Gen. Virol. 83: 311-316 [Abstract] [Full Text]
Lopez, D., Samino, Y., Koszinowski, U. H., Del Val, M. (2001). HIV Envelope Protein Inhibits MHC Class I Presentation of a Cytomegalovirus Protective Epitope. J. Immunol. 167: 4238-4244 [Abstract] [Full Text]
Kavanagh, D. G., Gold, M. C., Wagner, M., Koszinowski, U. H., Hill, A. B. (2001). The Multiple Immune-evasion Genes of Murine Cytomegalovirus Are Not Redundant: m4 and m152 Inhibit Antigen Presentation In a Complementary and Cooperative Fashion. J. Exp. Med. 194: 967-978 [Abstract] [Full Text]
Kavanagh, D. G., Koszinowski, U. H., Hill, A. B. (2001). The Murine Cytomegalovirus Immune Evasion Protein m4/gp34 Forms Biochemically Distinct Complexes with Class I MHC at the Cell Surface and in a Pre-Golgi Compartment. J. Immunol. 167: 3894-3902 [Abstract] [Full Text]
Morello, C. S., Cranmer, L. D., Spector, D. H. (2000). Suppression of Murine Cytomegalovirus (MCMV) Replication with a DNA Vaccine Encoding MCMV M84 (a Homolog of Human Cytomegalovirus pp65). J. Virol. 74: 3696-3708 [Abstract] [Full Text]
Holtappels, R., Thomas, D., Podlech, J., Geginat, G., Steffens, H.-P., Reddehase, M. J. (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: 1871-1884 [Abstract] [Full Text]
Sester, M., Feuerbach, D., Frank, R., Preckel, T., Gutermann, A., Burgert, H.-G. (2000). The Amyloid Precursor-like Protein 2 Associates with the Major Histocompatibility Complex Class I Molecule Kd. J. Biol. Chem. 275: 3645-3654 [Abstract] [Full Text]
Krmpotic, A., Messerle, M., Crnkovic-Mertens, I., Polic, B., Jonjic, S., Koszinowski, U. H. (1999). The Immunoevasive Function Encoded by the Mouse Cytomegalovirus Gene m152 Protects the Virus Against T Cell Control In Vivo. J. Exp. Med. 190: 1285-1296 [Abstract] [Full Text]
Cretney, E., Degli-Esposti, M. A., Densley, E. H., Farrell, H. E., Davis-Poynter, N. J., Smyth, M. J. (1999). m144, a Murine Cytomegalovirus (MCMV)-encoded Major Histocompatibility Complex Class I Homologue, Confers Tumor Resistance to Natural Killer Cell�mediated Rejection. J. Exp. Med. 190: 435-444 [Abstract] [Full Text]
Lin, X., Roos, R. P., Pease, L. R., Wettstein, P., Rodriguez, M. (1999). A Theiler's Virus Alternatively Initiated Protein Inhibits the Generation of H-2K-Restricted Virus-Specific Cytotoxicity. J. Immunol. 162: 17-24 [Abstract] [Full Text]
Gil-Torregrosa, B. C., Raul Castano, A., Del �Val, M. (1998). Major Histocompatibility Complex Class I Viral Antigen Processing in the Secretory Pathway Defined by the trans-Golgi Network Protease Furin. J. Exp. Med. 188: 1105-1116 [Abstract] [Full Text]
Holtappels, R., Podlech, J., Geginat, G., Steffens, H.-P., Thomas, D., Reddehase, M. J. (1998). Control of Murine Cytomegalovirus in the Lungs: Relative but Not Absolute Immunodominance of the Immediate-Early 1�Nonapeptide during the Antiviral Cytolytic T-Lymphocyte Response in Pulmonary Infiltrates. J. Virol. 72: 7201-7212 [Abstract] [Full Text]
Heise, M. T., Connick, M., Virgin IV, H. W. (1998). Murine Cytomegalovirus Inhibits Interferon gamma -induced Antigen Presentation to CD4 T Cells by Macrophages Via Regulation of Expression of Major Histocompatibility Complex Class II-associated Genes. J. Exp. Med. 187: 1037-1046 [Abstract] [Full Text]
Steffens, H.-P., Kurz, S., Holtappels, R., Reddehase, M. J. (1998). Preemptive CD8 T-Cell Immunotherapy of Acute Cytomegalovirus Infection Prevents Lethal Disease, Limits the Burden of Latent Viral Genomes, and Reduces the Risk of Virus Recurrence. J. Virol. 72: 1797-1804 [Abstract] [Full Text]
MacDonald, M. R., Li, X.-Y., Stenberg, R. M., Campbell, A. E., Virgin, H. W. IV (1998). Mucosal and Parenteral Vaccination against Acute and Latent Murine Cytomegalovirus (MCMV) Infection by Using an Attenuated MCMV Mutant. J. Virol. 72: 442-451 [Abstract] [Full Text]
Pantaleo, G., Soudeyns, H., Demarest, J. F., Vaccarezza, M., Graziosi, C., Paolucci, S., Daucher, M., Cohen, O. J., Denis, F., Biddison, W. E., Sekaly, R. P., Fauci, A. S. (1997). Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV�infection. Proc. Natl. Acad. Sci. USA 94: 9848-9853 [Abstract] [Full Text]
Machold, R. P., Wiertz, E. J.H.J., Jones, T. R., Ploegh, H.L. (1997). The HCMV Gene Products US11 and US2 Differ in Their Ability to Attack Allelic Forms of Murine Major Histocompatibility Complex (MHC) Class I Heavy Chains. J. Exp. Med. 185: 363-366 [Abstract] [Full Text]
Bubeck, A., Reusch, U., Wagner, M., Ruppert, T., Muranyi, W., Kloetzel, P. M., Koszinowski, U. H. (2002). The Glycoprotein gp48 of Murine Cytomegalovirus. PROTEASOME-DEPENDENT CYTOSOLIC DISLOCATION AND DEGRADATION. J. Biol. Chem. 277: 2216-2224 [Abstract] [Full Text]