Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2011 Jun 26;54(6):502–512. doi: 10.1007/s11427-011-4177-7

Viral proteomics: The emerging cutting-edge of virus research

ShengTao Zhou 1,2, Rui Liu 2, Xia Zhao 1,✉, CanHua Huang 2,✉, YuQuan Wei 2
PMCID: PMC7089374  PMID: 21706410

Abstract

Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment. They encode a wide spectrum of multifunctional proteins, which interplay with and modify proteins in host cells. Viral genomes were chronologically the first to be sequenced. However, the corresponding viral proteomes, the alterations of host proteomes upon viral infection, and the dynamic nature of proteins, such as post-translational modifications, enzymatic cleavage, and activation or destruction by proteolysis, remain largely unknown. Emerging high-throughput techniques, in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes, have been applied to define viruses and their interactions with their hosts. Here, we review the major areas of viral proteomics, including virion proteomics, structural proteomics, viral protein interactomics, and changes to the host cell proteome upon viral infection.

Keywords: virus, proteomics, virion proteomics, virus host interaction

Footnotes

Contributed equally to this work

This article is published with open access at Springerlink.com

Contributor Information

Xia Zhao, Email: xia-zhao@126.com.

CanHua Huang, Email: hcanhua@hotmail.com.

References

  • 1.Karen L. M., Lori F. Viral proteomics. Microbiol Mol Biol Rev. 2007;71:398–411. doi: 10.1128/MMBR.00042-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Yuan K., Lei Y. L., Huang C. Application of chemistry-based functional proteomics to screening for novel drug targets. Comb Chem High Throughput Screen. 2010;13:414–421. doi: 10.2174/138620710791292976. [DOI] [PubMed] [Google Scholar]
  • 3.Liu R., Bai S. J., Li Z. J., et al. Mechanism of cancer cell adaptation to metabolic stress: proteomics identification of a novel thyroid hormone-mediated gastric carcinogenic signalling pathway. Mol Cell Proteomics. 2009;8:70–85. doi: 10.1074/mcp.M800195-MCP200. [DOI] [PubMed] [Google Scholar]
  • 4.Miklos G L, Maleszka R. Protein functions and biological contexts. Proteomics, 2001: 169–178 [DOI] [PubMed]
  • 5.Nair K. S., Asmann Y. W., Short K. R., et al. Proteomic research: potential opportunities for clinical and physiological investigators. Am J Physiol Endocrinol Metab. 2004;286:863–874. doi: 10.1152/ajpendo.00370.2003. [DOI] [PubMed] [Google Scholar]
  • 6.Fields B. N., Howley P. M. Principles of Virus Structure. 3rd ed. Williams & Willkins: Philadelphia: Lippincott; 1996. Fundamental virology; pp. 59–100. [Google Scholar]
  • 7.Kalkkinen N., Soderlund H., Kaariainen L. Analysis of semliki-forest-virus structural proteins to illustrate polyprotein processing of alpha viruses. Eur J Biochem. 1980;108:31–37. doi: 10.1111/j.1432-1033.1980.tb04692.x. [DOI] [PubMed] [Google Scholar]
  • 8.Chelius D., Shieh C. H., Lehmberg E., et al. Analysis of the adenovirus type 5 proteome by liquid chromatography and tandem mass spectrometry methods. J Proteome Res. 2002;1:501–513. doi: 10.1021/pr025528c. [DOI] [PubMed] [Google Scholar]
  • 9.Davison A. J., Davison M. D. Identification of structural proteins of channel catfish virus by mass spectrometry. Virology. 1995;206:1035–1043. doi: 10.1006/viro.1995.1026. [DOI] [PubMed] [Google Scholar]
  • 10.Resch W. G., Moore R. J., Lipton M. S., et al. Protein composition of the vaccinia virus mature virion. Virology. 2007;358:233–247. doi: 10.1016/j.virol.2006.08.025. [DOI] [PubMed] [Google Scholar]
  • 11.Chung C. S., Ho M. Y., Huang C. Y., et al. Vaccinia virus proteome: identification of proteins in vaccinia virus intracellular mature virion particles. J Virol. 2006;80:2127–2140. doi: 10.1128/JVI.80.5.2127-2140.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Yoder J. D., Gagnier C. R., Vemulapalli S., et al. Pox proteomics: mass spectrometry analysis and identification of Vaccinia virion proteins. Virol J. 2006;3:10–26. doi: 10.1186/1743-422X-3-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Baldick C. J., Shenk T. Proteins associated with purified human cytomegalovirus particles. J Virol. 1996;70:6097–6105. doi: 10.1128/jvi.70.9.6097-6105.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kattenhorn L. M., Wagner M., Lomsadze A., et al. Identification of proteins associated with murine cytomegalovirus virions. J Virol. 2004;78:11187–11197. doi: 10.1128/JVI.78.20.11187-11197.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Johannsen E., Chase M. R., Weicksel S., et al. Proteins of purified Epstein-Barr virus. Proc Natl Acad Sci USA. 2004;101:16286–16291. doi: 10.1073/pnas.0407320101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Zhu F. X., Wu L. J., Yuan Y. Virion proteins of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2005;79:800–811. doi: 10.1128/JVI.79.2.800-811.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.O’Connor C. M., Kedes D. H. Mass spectrometric analyses of purified Rhesus monkey rhadinovirus reveal 33 virion-associated proteins. J Virol. 2006;80:1574–1583. doi: 10.1128/JVI.80.3.1574-1583.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Huang C. H., Lin Q. S., Xu X., et al. Proteomic analysis of shrimp white spot syndrome viral proteins and characterization of a novel envelope protein VP466. Mol Cell Proteomics. 2002;1:223–231. doi: 10.1074/mcp.M100035-MCP200. [DOI] [PubMed] [Google Scholar]
  • 19.Li Z., Chen J., Wu J. L., et al. Shotgun identification of the structural proteome of shrimp white spot syndrome virus and iTRAQ differentiation of envelope and nucleocapsid subproteomes. Mol Cell Proteomics. 2007;6:1609–1620. doi: 10.1074/mcp.M600327-MCP200. [DOI] [PubMed] [Google Scholar]
  • 20.Zeng R., Jiang X. S., Zhou H., et al. Proteomic analysis of SARS associated coronavirus using two-dimensional liquid chromatography mass spectrometry and one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by mass spectroemtric analysis. J Proteome Res. 2004;3:549–555. doi: 10.1021/pr034111j. [DOI] [PubMed] [Google Scholar]
  • 21.Saphire A. C., Bark S. J. Proteomic analysis of human immunodeficiency virus using liquid chromatography/tandem mass spectrometry effectively distinguishes specific incorporated host proteins. J Proteome Res. 2006;5:530–538. doi: 10.1021/pr050276b. [DOI] [PubMed] [Google Scholar]
  • 22.Chertova E., Coren L. V., Roser J. D., et al. Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages. J Virol. 2006;80:9039–9052. doi: 10.1128/JVI.01013-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Bortz E., Whitelegge J. P., Jia Q. M., et al. Identification of proteins associated with murine gammaherpesvirus 68 virions. J Virol. 2003;77:13425–13432. doi: 10.1128/JVI.77.24.13425-13432.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Varnum S. M., Monroe M. E., Smith P., et al. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol. 2004;78:10960–10966. doi: 10.1128/JVI.78.20.10960-10966.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Rozen R., Li Y., Yuan Y. Virion-wide protein interactions of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2008;82:4742–4750. doi: 10.1128/JVI.02745-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Bartel P. L., Roecklein J. A., SenGupta D., et al. Host and viral proteins in the virion of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2005;79:4952–4964. doi: 10.1128/JVI.79.8.4952-4964.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Vliet K. V., Zhang L. L., Villa N. Y., et al. Poxvirus proteomics and virushost protein interactions. Microbiol Mol Biol Rev. 2009;73:730–749. doi: 10.1128/MMBR.00026-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Oliver K. B., Russel J. D., Anthony L. C. New insights into viral structure and virus-cell interactions through proteomics. Expert Rev Proteomics. 2005;2:577–588. doi: 10.1586/14789450.2.4.577. [DOI] [PubMed] [Google Scholar]
  • 29.Bortz E., Whitelegge J. P., Jia Q., et al. Identification of proteins associated with murine gammaherpesvirus 68 virions. J Virol. 2003;77:13425–13432. doi: 10.1128/JVI.77.24.13425-13432.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Ying W. T., Zhang Y. J., Peng W. M., et al. Proteomic analysis on structural proteins of severe acute respiratory syndrome coronavirus. Proteomics. 2004;4:492–504. doi: 10.1002/pmic.200300676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Savalia D., Westblade L. F., Goel M., et al. Genomic and proteomic Analysis of phiEco32, a novel Esacherichia coli bacteriophage. J Mol Biol. 2008;377:774–789. doi: 10.1016/j.jmb.2007.12.077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Robert M. D., Martin N. L., Kropinski A. M. The genome and proteome of coliphage T1. Virology. 2004;318:245–266. doi: 10.1016/j.virol.2003.09.020. [DOI] [PubMed] [Google Scholar]
  • 33.Naryshkina T., Liu J., Florens L., et al. Thermus thermophilus bacteriophage phiYS40 genome and proteomic characterization of virions. J Mol Biol. 2006;364:667–677. doi: 10.1016/j.jmb.2006.08.087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Beijerinck M. J. Concerning a contagium vivum fluidum as cause of the spot disease of tobacco leaves. Verhandelingen der Koninkyke akademie Wettenschapppen te Amsterdam. 1898;65:3–21. [Google Scholar]
  • 35.Fields S., Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989;340:245–246. doi: 10.1038/340245a0. [DOI] [PubMed] [Google Scholar]
  • 36.Fields S. Interactive learning: Lessons from two hybrids over two decades. Proteomics. 2009;9:5209–5213. doi: 10.1002/pmic.200900236. [DOI] [PubMed] [Google Scholar]
  • 37.Mendez-Rios J., Uetz P. Global approaches to study protein-protein interactions among viruses and hosts. Future Microbiol. 2010;5:289–301. doi: 10.2217/fmb.10.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Bartel P. L., SenGupta D., Fields S. A protein linkage map of Escherichia coli bacteriophage T7. Nat Genet. 1996;12:72–77. doi: 10.1038/ng0196-72. [DOI] [PubMed] [Google Scholar]
  • 39.McCraith S., Moss B., Fields S. Genome-wide analysis of vaccinia virus protein-protein interactions. Proc Natl Acad Sci USA. 2000;97:4879–4884. doi: 10.1073/pnas.080078197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Dziembowski A., Ventura A. P., Rutz B., et al. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 2004;23:4847–4856. doi: 10.1038/sj.emboj.7600482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Jorba N., Torreira E., Gastaminza P., et al. Analysis of the interaction of influenza virus polymerase complex with human cell factors. Proteomics. 2008;8:2077–2088. doi: 10.1002/pmic.200700508. [DOI] [PubMed] [Google Scholar]
  • 42.Mayer D., Martinez-Sobrido L., Ghanem A., et al. Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approaches. J Proteome Res. 2007;6:672–682. doi: 10.1021/pr060432u. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Molina-Jiménez F., Murata M., Martín-Vílchez S., et al. Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation. Hepatol. 2010;51:777–787. doi: 10.1002/hep.23468. [DOI] [PubMed] [Google Scholar]
  • 44.Cristea I. M., Carroll J. N., Rout M. P., et al. Tracking and elucidating alphavirus-host protein interactions. J Biol Chem. 2006;281:30269–30278. doi: 10.1074/jbc.M603980200. [DOI] [PubMed] [Google Scholar]
  • 45.Hirsch A. J. The use of RNAi-based screens to identify host proteins involved in viral replication. Future Microbiol. 2010;5:303–311. doi: 10.2217/fmb.09.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Brass A. L., Dykxhoor D. M., Benita Y., et al. Identification of host proteins required for HIV infection through a functional genomics screen. Science. 2008;319:921–926. doi: 10.1126/science.1152725. [DOI] [PubMed] [Google Scholar]
  • 47.Konig R., Zhou Y. Y., Elleder D., et al. Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell. 2008;135:49–60. doi: 10.1016/j.cell.2008.07.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Tong A. P., Gou L. T., Lau Q. C., et al. Proteomic profiling identifies aberrant epigenetic modifications induced by hepatitis B virus X protein. J Proteome Res. 2009;8:1037–1046. doi: 10.1021/pr8008622. [DOI] [PubMed] [Google Scholar]
  • 49.Toda T., Sugimoto M., Omori A., et al. Proteomic analysis of Epstein-Barr virus-transformed human B-lymphoblastiod cell lines before and after immortalization. Electrophoresis. 2000;21:1814–1822. doi: 10.1002/(SICI)1522-2683(20000501)21:9<1814::AID-ELPS1814>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  • 50.Coiras M., Camafeita E., Urena T., et al. Modifications in the human T cell proteome induced by intracellular HIV-1 Tat protein expression. Proteomics. 2006;6:S63–S73. doi: 10.1002/pmic.200500437. [DOI] [PubMed] [Google Scholar]
  • 51.Chen X., Yu Y. B., Xue Y., et al. Amino acid-coded tagging approaches in quantitative proteomics. Expert Rev Proteomics. 2007;4:25–37. doi: 10.1586/14789450.4.1.25. [DOI] [PubMed] [Google Scholar]
  • 52.Mannova P., Wang H., Deng B., et al. Modification of host lipid raft proteome upon hepatitis C virus replication. Mol Cell Proteomics. 2006;5:2319–2325. doi: 10.1074/mcp.M600121-MCP200. [DOI] [PubMed] [Google Scholar]
  • 53.Zhang L., Zhang X. E., Lin F. S., et al. Quantitative proteomics analysis reveals BAG3 as a potential target to suppress severe acute respiratory syndrome coronavirus replication. J Virol. 2010;84:6050–6059. doi: 10.1128/JVI.00213-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Booy A. T., Ohlund L. B., Hardie D. B., et al. Application of isotope coded affinity tag (ICAT) analysis for the identification of differentially expressed proteins following infection of atlantic salmon (Salmo salar) with infectious hematopoietic necrosis virus (IHNV) or Renibacterium salmoninarum (BKD) J Proteome Res. 2005;4:325–334. doi: 10.1021/pr049840t. [DOI] [PubMed] [Google Scholar]
  • 55.Go E. P., Wikoff W. R., Shen Z., et al. Mass spectrometry reveals specific and global molecular transformations during viral infection. J Proteome Res. 2006;5:2405–2416. doi: 10.1021/pr060215t. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Jiang X. S., Tang L. Y., Dai J., et al. Quantitative analysis of severe acute respiratory syndrome (SARS)-associated coronavirus-infected cells using proteomic approach. Mol Cell Proteomics. 2005;4:902–913. doi: 10.1074/mcp.M400112-MCP200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Chen L. M., Lin Q. S., Lim T. K., et al. iTRAQ analysis of Singapore grouper iridovirus infection in a grouper embryonic cell line. J General Virol. 2008;89:2869–2876. doi: 10.1099/vir.0.2008/003681-0. [DOI] [PubMed] [Google Scholar]
  • 58.Diamond D. L., Jacobs J. M., Paeper B., et al. Proteomic profiling of human liver biopsies: hepatitis C virus-induced fibrosis and mitochondrial dysfunction. Hepatol. 2007;46:649–657. doi: 10.1002/hep.21751. [DOI] [PubMed] [Google Scholar]
  • 59.Chan E. Y., Qian W. J., Diamond D. L., et al. Quantitative analysis of HIV-1 infected CD4+ cell proteome: dysregulated cell cycle progression and nuclear transport coincide with robust virus production. J Virol. 2007;81:7571–7583. doi: 10.1128/JVI.00288-07. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Science China. Life Sciences are provided here courtesy of Nature Publishing Group

RESOURCES