Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection

ABSTRACT

The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus–host protein–protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus–host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus–host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted.

KEYWORDS:

• virus–host interactions
• mass spectrometry
• viral proteomics
• AP-MS
• IP-MS
• interactome

Acknowledgement

The authors are grateful for funding from the National Institutes of Health, grants R01 [GM114141] and R21 [AI102187] to IM Cristea.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key Issues

• Successful virus replication and pathogenesis depend upon dynamic virus–host protein–protein interactions within a permissive cell.

• The continued development and use of proteomic techniques, including antibody-based affinity purifications, cross-linking, MS, and protein arrays, have afforded novel biological discoveries pertaining to the mechanisms by which viruses progress through their life cycles and hosts mount defenses.

• Epitope tagging within either replication-competent virus strains or single viral proteins has facilitated the identification of temporally and spatially regulated virus–host interactions by immunoaffinity purification coupled to MS.

• Characterizing virus–host protein interactions can uncover new targets for the development of therapies to predict, prevent, or treat virus-induced illnesses.

• Proteomics can be readily integrated with orthogonal approaches, such as biochemical, optical, and molecular virology methods. These multi-disciplinary studies are expected to contribute significantly to future discoveries in virology.