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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.



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