Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jun 15:218:25-39.
doi: 10.1016/j.virusres.2015.09.006. Epub 2015 Sep 10.

Decoding protein networks during virus entry by quantitative proteomics

Gisa Gerold  1 , Janina Bruening  2 , Thomas Pietschmann  3
Affiliations
Review

Decoding protein networks during virus entry by quantitative proteomics

Gisa Gerold et al. Virus Res. .

Abstract

Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.

Keywords: Protein interaction networks; Protein–protein interactions; Quantitative proteomics; Virus entry.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Timeline of the milestones in virus entry research and pioneering MS technology development.
Fig. 2
Fig. 2
Schematic representation of virus entry pathways. PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating. Classical virus infection pathways are illustrated for a generic enveloped virus. Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown). PPIs facilitating virus attachment, surfing, fusion and transport are depicted. In some cases proteolytic processing mediated by host factors triggers viral membrane fusion. Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.
Fig. 3
Fig. 3
High resolution quantitative MS-based interaction proteomics using stable isotope labeling (A) or label-free (B) technologies. Consecutive quality control steps (C) and follow up analysis (D) are indicated.
Fig. 4
Fig. 4
Interaction proteomics based systems virology workflow.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aloy P., Russell R.B. Ten thousand interactions for the molecular biologist. Nat. Biotechnol. 2004;22:1317–1321. - PubMed
    1. Amara A., Mercer J. Viral apoptotic mimicry. Nat. Rev. Microbiol. 2015;13:461–469. - PMC - PubMed
    1. Amstutz B., Gastaldelli M., Kalin S., Imelli N., Boucke K., Wandeler E., Mercer J., Hemmi S., Greber U.F. Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3. EMBO J. 2008;27:956–969. - PMC - PubMed
    1. Andersen J.S., Matic I., Vertegaal A.C. Identification of SUMO target proteins by quantitative proteomics. Methods Mol. Biol. 2009;497:19–31. - PubMed
    1. Berard A.R., Coombs K.M., Severini A. Quantification of the host response proteome after herpes simplex virus type 1 infection. J. Proteome Res. 2015;14:2121–2142. - PubMed

Publication types

MeSH terms