This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Varnum, S. M.
Right arrow Articles by Nelson, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varnum, S. M.
Right arrow Articles by Nelson, J. A.

 Previous Article  |  Next Article 

Journal of Virology, October 2004, p. 10960-10966, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10960-10966.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome{dagger}

Susan M. Varnum,1,{ddagger} Daniel N. Streblow,2*,{ddagger} Matthew E. Monroe,1 Patricia Smith,2 Kenneth J. Auberry,1 Ljiljana Pasa-Toli,1 Dai Wang,3 David G. Camp II,1 Karin Rodland,1 Steven Wiley,1 William Britt,4 Thomas Shenk,3 Richard D. Smith,1 and Jay A. Nelson2

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington,1 Vaccine and Gene Therapy Institute and Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon,2 Department of Molecular Biology, Princeton University, Princeton, New Jersey,3 Department of Pediatrics, University of Alabama, Birmingham, Alabama4

Received 8 April 2004/ Accepted 4 June 2004

Human cytomegalovirus (HCMV), a member of the herpesvirus family, is a large complex enveloped virus composed of both viral and cellular gene products. While the sequence of the HCMV genome has been known for over a decade, the full set of viral and cellular proteins that compose the HCMV virion are unknown. To approach this problem we have utilized gel-free two-dimensional capillary liquid chromatography-tandem mass spectrometry (MS/MS) and Fourier transform ion cyclotron resonance MS to identify and determine the relative abundances of viral and cellular proteins in purified HCMV AD169 virions and dense bodies. Analysis of the proteins from purified HCMV virion preparations has indicated that the particle contains significantly more viral proteins than previously known. In this study, we identified 71 HCMV-encoded proteins that included 12 proteins encoded by known viral open reading frames (ORFs) previously not associated with virions and 12 proteins from novel viral ORFs. Analysis of the relative abundance of HCMV proteins indicated that the predominant virion protein was the pp65 tegument protein and that gM rather than gB was the most abundant glycoprotein. We have also identified over 70 host cellular proteins in HCMV virions, which include cellular structural proteins, enzymes, and chaperones. In addition, analysis of HCMV dense bodies indicated that these viral particles are composed of 29 viral proteins with a reduced quantity of cellular proteins in comparison to HCMV virions. This study provides the first comprehensive quantitative analysis of the viral and cellular proteins that compose infectious particles of a large complex virus.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201. Phone: (503) 418-4038. Fax: (503) 418-2719. E-mail: streblow{at}ohsu.edu.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} S.M.V. and D.N.S. contributed equally to this work.

Journal of Virology, October 2004, p. 10960-10966, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10960-10966.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Berndt, A., Hofmann-Winkler, H., Tavalai, N., Hahn, G., Stamminger, T. (2009). Importance of Covalent and Noncovalent SUMO Interactions with the Major Human Cytomegalovirus Transactivator IE2p86 for Viral Infection. J. Virol. 83: 12881-12894 [Abstract] [Full Text]  
  • Wang, S.-K., Hu, C.-H., Lu, M.-C., Duh, C.-Y., Liao, P.-C., Tyan, Y.-C. (2009). Novel virus-associated proteins encoded by UL112-113 of human cytomegalovirus. J. Gen. Virol. 90: 2840-2848 [Abstract] [Full Text]  
  • Buchkovich, N. J., Maguire, T. G., Paton, A. W., Paton, J. C., Alwine, J. C. (2009). The Endoplasmic Reticulum Chaperone BiP/GRP78 Is Important in the Structure and Function of the Human Cytomegalovirus Assembly Compartment. J. Virol. 83: 11421-11428 [Abstract] [Full Text]  
  • Groves, I. J., Reeves, M. B., Sinclair, J. H. (2009). Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic 'pre-immediate-early' repression of viral gene expression mediated by histone post-translational modification. J. Gen. Virol. 90: 2364-2374 [Abstract] [Full Text]  
  • Mitchell, D. P., Savaryn, J. P., Moorman, N. J., Shenk, T., Terhune, S. S. (2009). Human Cytomegalovirus UL28 and UL29 Open Reading Frames Encode a Spliced mRNA and Stimulate Accumulation of Immediate-Early RNAs. J. Virol. 83: 10187-10197 [Abstract] [Full Text]  
  • Burkhardt, C., Himmelein, S., Britt, W., Winkler, T., Mach, M. (2009). Glycoprotein N subtypes of human cytomegalovirus induce a strain-specific antibody response during natural infection. J. Gen. Virol. 90: 1951-1961 [Abstract] [Full Text]  
  • Petrucelli, A., Rak, M., Grainger, L., Goodrum, F. (2009). Characterization of a Novel Golgi Apparatus-Localized Latency Determinant Encoded by Human Cytomegalovirus. J. Virol. 83: 5615-5629 [Abstract] [Full Text]  
  • Padula, M. E., Sydnor, M. L., Wilson, D. W. (2009). Isolation and Preliminary Characterization of Herpes Simplex Virus 1 Primary Enveloped Virions from the Perinuclear Space. J. Virol. 83: 4757-4765 [Abstract] [Full Text]  
  • Isaacson, M. K., Compton, T. (2009). Human Cytomegalovirus Glycoprotein B Is Required for Virus Entry and Cell-to-Cell Spread but Not for Virion Attachment, Assembly, or Egress. J. Virol. 83: 3891-3903 [Abstract] [Full Text]  
  • Chevillotte, M., Landwehr, S., Linta, L., Frascaroli, G., Luske, A., Buser, C., Mertens, T., von Einem, J. (2009). Major Tegument Protein pp65 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 [Abstract] [Full Text]  
  • Lyman, M. G., Enquist, L. W. (2009). Herpesvirus Interactions with the Host Cytoskeleton. J. Virol. 83: 2058-2066 [Full Text]  
  • Gao, Y., Pari, G. S. (2009). Interaction of Human Cytomegalovirus pUL84 with Casein Kinase 2 Is Required for oriLyt-Dependent DNA Replication. J. Virol. 83: 2393-2396 [Abstract] [Full Text]  
  • Walker, J. D., Maier, C. L., Pober, J. S. (2009). Cytomegalovirus-Infected Human Endothelial Cells Can Stimulate Allogeneic CD4+ Memory T Cells by Releasing Antigenic Exosomes. J. Immunol. 182: 1548-1559 [Abstract] [Full Text]  
  • Leege, T., Fuchs, W., Granzow, H., Kopp, M., Klupp, B. G., Mettenleiter, T. C. (2009). Effects of Simultaneous Deletion of pUL11 and Glycoprotein M on Virion Maturation of Herpes Simplex Virus Type 1. J. Virol. 83: 896-907 [Abstract] [Full Text]  
  • Crough, T., Khanna, R. (2009). Immunobiology of Human Cytomegalovirus: from Bench to Bedside. Clin. Microbiol. Rev. 22: 76-98 [Abstract] [Full Text]  
  • Wang, J. B., McVoy, M. A. (2008). Mutagenesis of the murine cytomegalovirus M56 terminase gene. J. Gen. Virol. 89: 2864-2868 [Abstract] [Full Text]  
  • Loret, S., Guay, G., Lippe, R. (2008). Comprehensive Characterization of Extracellular Herpes Simplex Virus Type 1 Virions. J. Virol. 82: 8605-8618 [Abstract] [Full Text]  
  • Seo, J.-Y., Britt, W. J. (2008). Multimerization of Tegument Protein pp28 within the Assembly Compartment Is Required for Cytoplasmic Envelopment of Human Cytomegalovirus. J. Virol. 82: 6272-6287 [Abstract] [Full Text]  
  • Kalejta, R. F. (2008). Tegument Proteins of Human Cytomegalovirus. Microbiol. Mol. Biol. Rev. 72: 249-265 [Abstract] [Full Text]  
  • Prichard, M. N., Sztul, E., Daily, S. L., Perry, A. L., Frederick, S. L., Gill, R. B., Hartline, C. B., Streblow, D. N., Varnum, S. M., Smith, R. D., Kern, E. R. (2008). Human Cytomegalovirus UL97 Kinase Activity Is Required for the Hyperphosphorylation of Retinoblastoma Protein and Inhibits the Formation of Nuclear Aggresomes. J. Virol. 82: 5054-5067 [Abstract] [Full Text]  
  • Borst, E. M., Wagner, K., Binz, A., Sodeik, B., Messerle, M. (2008). The Essential Human Cytomegalovirus Gene UL52 Is Required for Cleavage-Packaging of the Viral Genome. J. Virol. 82: 2065-2078 [Abstract] [Full Text]  
  • Lilja, A. E., Chang, W. L. W., Barry, P. A., Becerra, S. P., Shenk, T. E. (2008). Functional Genetic Analysis of Rhesus Cytomegalovirus: Rh01 Is an Epithelial Cell Tropism Factor. J. Virol. 82: 2170-2181 [Abstract] [Full Text]  
  • Mersseman, V., Besold, K., Reddehase, M. J., Wolfrum, U., Strand, D., Plachter, B., Reyda, S. (2008). Exogenous introduction of an immunodominant peptide from the non-structural IE1 protein of human cytomegalovirus into the MHC class I presentation pathway by recombinant dense bodies. J. Gen. Virol. 89: 369-379 [Abstract] [Full Text]  
  • Yamagishi, Y., Sadaoka, T., Yoshii, H., Somboonthum, P., Imazawa, T., Nagaike, K., Ozono, K., Yamanishi, K., Mori, Y. (2008). Varicella-Zoster Virus Glycoprotein M Homolog Is Glycosylated, Is Expressed on the Viral Envelope, and Functions in Virus Cell-to-Cell Spread. J. Virol. 82: 795-804 [Abstract] [Full Text]  
  • Gao, Y., Colletti, K., Pari, G. S. (2008). Identification of Human Cytomegalovirus UL84 Virus- and Cell-Encoded Binding Partners by Using Proteomics Analysis. J. Virol. 82: 96-104 [Abstract] [Full Text]  
  • Wagner, C. S., Ljunggren, H.-G., Achour, A. (2008). Immune Modulation by the Human Cytomegalovirus-Encoded Molecule UL18, a Mystery Yet to Be Solved. J. Immunol. 180: 19-24 [Abstract] [Full Text]  
  • Benach, J., Wang, L., Chen, Y., Ho, C. K., Lee, S., Seetharaman, J., Xiao, R., Acton, T. B., Montelione, G. T., Deng, H., Sun, R., Tong, L. (2007). Structural and Functional Studies of the Abundant Tegument Protein ORF52 from Murine Gammaherpesvirus 68. J. Biol. Chem. 282: 31534-31541 [Abstract] [Full Text]  
  • Zhang, G., Raghavan, B., Kotur, M., Cheatham, J., Sedmak, D., Cook, C., Waldman, J., Trgovcich, J. (2007). Antisense Transcription in the Human Cytomegalovirus Transcriptome. J. Virol. 81: 11267-11281 [Abstract] [Full Text]  
  • Krzyzaniak, M., Mach, M., Britt, W. J. (2007). The Cytoplasmic Tail of Glycoprotein M (gpUL100) Expresses Trafficking Signals Required for Human Cytomegalovirus Assembly and Replication. J. Virol. 81: 10316-10328 [Abstract] [Full Text]  
  • Colletti, K. S., Smallenburg, K. E., Xu, Y., Pari, G. S. (2007). Human Cytomegalovirus UL84 Interacts with an RNA Stem-Loop Sequence Found within the RNA/DNA Hybrid Region of oriLyt. J. Virol. 81: 7077-7085 [Abstract] [Full Text]  
  • Maxwell, K. L., Frappier, L. (2007). Viral Proteomics. Microbiol. Mol. Biol. Rev. 71: 398-411 [Abstract] [Full Text]  
  • Nogalski, M. T., Podduturi, J. P., DeMeritt, I. B., Milford, L. E., Yurochko, A. D. (2007). The Human Cytomegalovirus Virion Possesses an Activated Casein Kinase II That Allows for the Rapid Phosphorylation of the Inhibitor of NF-{kappa}B, I{kappa}B{alpha}. J. Virol. 81: 5305-5314 [Abstract] [Full Text]  
  • 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 pp65-derived peptides persist despite gpUS2-11-mediated immune evasion. J. Gen. Virol. 88: 1429-1439 [Abstract] [Full Text]  
  • Terhune, S., Torigoi, E., Moorman, N., Silva, M., Qian, Z., Shenk, T., Yu, D. (2007). Human Cytomegalovirus UL38 Protein Blocks Apoptosis. J. Virol. 81: 3109-3123 [Abstract] [Full Text]  
  • Lee, J. I-H., Luxton, G. W. G., Smith, G. A. (2006). Identification of an Essential Domain in the Herpesvirus VP1/2 Tegument Protein: the Carboxy Terminus Directs Incorporation into Capsid Assemblons. J. Virol. 80: 12086-12094 [Abstract] [Full Text]  
  • Feng, X., Schroer, J., Yu, D., Shenk, T. (2006). Human Cytomegalovirus pUS24 Is a Virion Protein That Functions Very Early in the Replication Cycle.. J. Virol. 80: 8371-8378 [Abstract] [Full Text]  
  • AuCoin, D. P., Smith, G. B., Meiering, C. D., Mocarski, E. S. (2006). Betaherpesvirus-Conserved Cytomegalovirus Tegument Protein ppUL32 (pp150) Controls Cytoplasmic Events during Virion Maturation.. J. Virol. 80: 8199-8210 [Abstract] [Full Text]  
  • Lorz, K., Hofmann, H., Berndt, A., Tavalai, N., Mueller, R., Schlotzer-Schrehardt, U., Stamminger, T. (2006). Deletion of Open Reading Frame UL26 from the Human Cytomegalovirus Genome Results in Reduced Viral Growth, Which Involves Impaired Stability of Viral Particles.. J. Virol. 80: 5423-5434 [Abstract] [Full Text]  
  • Seo, J.-Y., Britt, W. J. (2006). Sequence Requirements for Localization of Human Cytomegalovirus Tegument Protein pp28 to the Virus Assembly Compartment and for Assembly of Infectious Virus.. J. Virol. 80: 5611-5626 [Abstract] [Full Text]  
  • Sanchez, V., Spector, D. H. (2006). Cyclin-Dependent Kinase Activity Is Required for Efficient Expression and Posttranslational Modification of Human Cytomegalovirus Proteins and for Production of Extracellular Particles.. J. Virol. 80: 5886-5896 [Abstract] [Full Text]  
  • Shimamura, M., Mach, M., Britt, W. J. (2006). Human Cytomegalovirus Infection Elicits a Glycoprotein M (gM)/gN-Specific Virus-Neutralizing Antibody Response. J. Virol. 80: 4591-4600 [Abstract] [Full Text]  
  • Munger, J., Yu, D., Shenk, T. (2006). UL26-Deficient Human Cytomegalovirus Produces Virions with Hypophosphorylated pp28 Tegument Protein That Is Unstable within Newly Infected Cells.. J. Virol. 80: 3541-3548 [Abstract] [Full Text]  
  • Chung, C.-S., Chen, C.-H., Ho, M.-Y., Huang, C.-Y., Liao, C.-L., Chang, W. (2006). Vaccinia Virus Proteome: Identification of Proteins in Vaccinia Virus Intracellular Mature Virion Particles. J. Virol. 80: 2127-2140 [Abstract] [Full Text]  
  • Kolegraff, K., Bostik, P., Ansari, A. A. (2006). Characterization and role of lentivirus-associated host proteins.. Exp. Biol. Med. 231: 252-263 [Abstract] [Full Text]  
  • Das, S., Skomorovska-Prokvolit, Y., Wang, F.-Z., Pellett, P. E. (2006). Infection-Dependent Nuclear Localization of US17, a Member of the US12 Family of Human Cytomegalovirus-Encoded Seven-Transmembrane Proteins. J. Virol. 80: 1191-1203 [Abstract] [Full Text]  
  • Michael, K., Klupp, B. G., Mettenleiter, T. C., Karger, A. (2006). Composition of Pseudorabies Virus Particles Lacking Tegument Protein US3, UL47, or UL49 or Envelope Glycoprotein E. J. Virol. 80: 1332-1339 [Abstract] [Full Text]  
  • O'Connor, C. M., Kedes, D. H. (2006). Mass Spectrometric Analyses of Purified Rhesus Monkey Rhadinovirus Reveal 33 Virion-Associated Proteins. J. Virol. 80: 1574-1583 [Abstract] [Full Text]  
  • Ryckman, B. J., Jarvis, M. A, Drummond, D. D., Nelson, J. A., Johnson, D. C. (2006). Human Cytomegalovirus Entry into Epithelial and Endothelial Cells Depends on Genes UL128 to UL150 and Occurs by Endocytosis and Low-pH Fusion. J. Virol. 80: 710-722 [Abstract] [Full Text]  
  • Prichard, M. N., Britt, W. J., Daily, S. L., Hartline, C. B., Kern, E. R. (2005). Human Cytomegalovirus UL97 Kinase Is Required for the Normal Intranuclear Distribution of pp65 and Virion Morphogenesis. J. Virol. 79: 15494-15502 [Abstract] [Full Text]  
  • Wang, D., Shenk, T. (2005). Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc. Natl. Acad. Sci. USA 102: 18153-18158 [Abstract] [Full Text]  
  • Griffin, C., Wang, E. C. Y., McSharry, B. P., Rickards, C., Browne, H., Wilkinson, G. W. G., Tomasec, P. (2005). Characterization of a highly glycosylated form of the human cytomegalovirus HLA class I homologue gpUL18. J. Gen. Virol. 86: 2999-3008 [Abstract] [Full Text]  
  • Klupp, B. G., Granzow, H., Karger, A., Mettenleiter, T. C. (2005). Identification, Subviral Localization, and Functional Characterization of the Pseudorabies Virus UL17 Protein. J. Virol. 79: 13442-13453 [Abstract] [Full Text]  
  • Davison, A. J., Stow, N. D. (2005). New Genes from Old: Redeployment of dUTPase by Herpesviruses. J. Virol. 79: 12880-12892 [Abstract] [Full Text]  
  • Takemoto, M., Koike, M., Mori, Y., Yonemoto, S., Sasamoto, Y., Kondo, K., Uchiyama, Y., Yamanishi, K. (2005). Human Herpesvirus 6 Open Reading Frame U14 Protein and Cellular p53 Interact with Each Other and Are Contained in the Virion. J. Virol. 79: 13037-13046 [Abstract] [Full Text]  
  • Spaderna, S., Kropff, B., Kodel, Y., Shen, S., Coley, S., Lu, S., Britt, W., Mach, M. (2005). Deletion of gpUL132, a Structural Component of Human Cytomegalovirus, Results in Impaired Virus Replication in Fibroblasts. J. Virol. 79: 11837-11847 [Abstract] [Full Text]  
  • Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., Nelson, J. A., Picker, L. J. (2005). Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. JEM 202: 673-685 [Abstract] [Full Text]  
  • del Rio, T., DeCoste, C. J., Enquist, L.W. (2005). Actin Is a Component of the Compensation Mechanism in Pseudorabies Virus Virions Lacking the Major Tegument Protein VP22. J. Virol. 79: 8614-8619 [Abstract] [Full Text]  
  • Isler, J. A., Skalet, A. H., Alwine, J. C. (2005). Human Cytomegalovirus Infection Activates and Regulates the Unfolded Protein Response. J. Virol. 79: 6890-6899 [Abstract] [Full Text]  
  • Bechtel, J. T., Winant, R. C., Ganem, D. (2005). Host and Viral Proteins in the Virion of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 79: 4952-4964 [Abstract] [Full Text]  
  • Britt, W. J., Jarvis, M. A., Drummond, D. D., Mach, M. (2005). Antigenic Domain 1 Is Required for Oligomerization of Human Cytomegalovirus Glycoprotein B. J. Virol. 79: 4066-4079 [Abstract] [Full Text]  
  • Schierling, K., Buser, C., Mertens, T., Winkler, M. (2005). Human Cytomegalovirus Tegument Protein ppUL35 Is Important for Viral Replication and Particle Formation. J. Virol. 79: 3084-3096 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»